Zr-Based MOF-808 As Meerwein–Ponndorf–Verley Reduction Catalyst for Challenging Carbonyl Compounds

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Article Zr-Based MOF-808 as Meerwein–Ponndorf–Verley Reduction Catalyst for Challenging Carbonyl Compounds

Eva Plessers, Guangxia Fu, Collin Yong Xiang Tan, Dirk E. De Vos and Maarten B. J. Roeffaers * Centre for Surface Chemistry and Catalysis, KU Leuven, Celestijnenlaan 200F, 3001 Heverlee, Belgium; [email protected] (E.P.); [email protected] (G.F.); [email protected] (C.Y.X.T.); [email protected] (D.E.D.V.) * Correspondence: [email protected]; Tel.: +32-16-327-449

Academic Editor: Minhua Shao Received: 13 June 2016; Accepted: 13 July 2016; Published: 19 July 2016 Abstract: In the ﬁne chemical industry, transfer hydrogenation of carbonyl compounds is an important route to selectively form the corresponding allyl alcohol. The Meerwein–Ponndorf–Verley reduction (MPV) is catalyzed by a Lewis acid catalyst and easily oxidizable alcohols serve as hydrogen donor. We successfully used the Zr-based metal-organic framework (MOF) MOF-808-P as MPV-catalyst with isopropyl alcohol as solvent and hydride donor. After only 2 h, 99% yield of cinnamyl alcohol was obtained. The highly active MOF-808-P is also a good catalyst for the selective reduction of more challenging substrates such as R-carvone and β-ionone. Two strategies were successfully used to shift the equilibrium towards the desired allylic alcohol products: (1) evaporation of formed acetone and (2) the use of the more strongly reducing 1-indanol. Carveol yield was increased to >70%. These results highlight the great potential of this recently discovered Zr-MOF as a chemically and thermally stable catalyst.

Keywords: chemoselective catalytic reduction; Meerwein–Ponndorf–Verley; metal-organic framework; heterogeneous Lewis acid; unsaturated aldehyde and ketone; MOF-808

1. Introduction In the fragrance and pharmaceutical industry, allylic alcohols are important intermediates and ﬂavoring compounds [1]. A widespread route to obtaining these allylic alcohols is via the chemoselective reduction of unsaturated aldehydes and ketones. This reduction can be performed via hydrogen transfer from easily oxidizable alcohols catalyzed by a Lewis acid or basic catalyst, a procedure called Meerwein–Ponndorf–Verley reduction (MPV) [2]. MPV reductions are typically performed under mild conditions and with high chemoselectivity because of the low risk of reducing other functional groups or unsaturated C=C-bonds. The high selectivity can be explained by the mechanism in which a cyclic six-membered transition state is formed [3,4]. Hydrogen donor and acceptor coordinate simultaneously to the Lewis acidic metal center; via this coordination, the carbonyl group of the substrate is activated for the hydride transfer and the reduction is performed with high selectivity [5]. Isopropyl alcohol (IPA) is the most widely used hydride donor because it is easily oxidized to acetone and is environmentally friendly [6]. The major disadvantage of IPA, however, is the reversibility of the reaction [7]. The reverse complementary oxidation of alcohols is known as the Oppenauer oxidation, resulting in an equilibrium called the Meerwein–Ponndorf–Verley–Oppenauer (MPVO) redox equilibrium [5]. To direct the equilibrium towards the desired allylic alcohol, IPA is often used in excess as the solvent of the reaction. The earliest reported MPV-catalysts were aluminum alkoxides [8]; recent improvements of these homogeneous aluminum catalysts lead to the development of highly efﬁcient aluminum

Catalysts 2016, 6, 104; doi:10.3390/catal6070104 www.mdpi.com/journal/catalysts Catalysts 2016, 6, 104 2 of 11 siloxide [9] and enantioselective calixarene-based MPV-catalysts [10,11]. However, in the last 15 years, zirconium-based catalysts are gaining interest [3,7,12–15]. The earliest reported Zr-catalysts were unsupported zirconia. In the MPVO reaction of ethanol and acetone, the weakly basic ZrO2 performed less well than the strongly basic MgO [16]. Hydrous zirconia, on the other hand, proved to be a good MPV-catalyst, giving a 78% cinnamyl alcohol yield [3], and could be used under flow conditions [17]. Grafting of Zr on siliceous SBA-15 (SBA for Santa Barbara Amorphous type material) or zeolite Beta dramatically decreased the necessary Zr/substrate ratio [18–20]. The Zr-zeolite Beta catalyst—with Zr substituted isomorphously into the lattice—was reusable, stable in water, and only 1.3 mol % Zr was used to reach 96% cinnamyl alcohol yield within reasonable reaction time. Lewis acidity of the Zr-atoms in zeolite Beta was increased by a two-step post-synthesis method to reach 100% cinnamyl alcohol yield [21]. Cinnamaldehyde is one of the most widely used α,β-unsaturated aldehydes. It is an attractive MPV-substrate since the unsaturated alcohol product is used as a flowery note [3], and as raw material in the fragrance and pharmaceutical industry—e.g., for the cardiovascular drug cinnarizine, which is derived from cinnamyl alcohol [22]. Another reason for studying cinnamaldehyde as a reactant is the fact that it is relatively easily reduced chemoselectively compared to other unsaturated aldehydes or ketones because of favorable steric and electronic properties. Citral is another widely studied MPV-substrate for which typically lower yields are reached, so longer reaction time or higher Zr-loadings are necessary [15,19,21,23]. Carvone, isophorone, and β-ionone are examples of α,β-unsaturated ketones that are even more difficult to chemoselectively reduce to obtain allylic alcohols in high yields. De bruyn, et al. [7,24], however, overcame this limitation by using the more strongly reducing 1-indanol as hydrogen donor and siliceous MCM-41 (MCM for Mobil Crystalline Material) immobilized Zr and Hf as catalysts. Aside from zeolites and mesoporous silicas, Zr-containing metal-organic frameworks (MOFs) have recently been proposed as MPV-catalysts. MOFs are crystalline, porous materials composed of metal (oxide) nodes interlinked by polytopic organic ligands, forming three-dimensional structures with well-defined cages and channels. These microporous solids have attracted researchers’ interest mainly due to their versatility, high surface area, and acid–base properties. Even though concerns have been raised about their thermal and physical stability, MOFs are promising catalysts for the synthesis of high-added-value products [25–27]. UiO-66 (UiO for University of Oslo) is a zirconium-terephthalate-based MOF best known for its high chemical and thermal stability and easy functionalization. When HCl and/or trifluoroacetic acid are added to the MOF synthesis mixture, terephthalate linkers are partially replaced by trifluoroacetate, resulting in a more open framework with a large number of open sites [14]. These Zr-based modulated UiO-66 and UiO-66-NO2 were already successfully used as MPV reduction catalysts with tert-butylcyclohexanone as the reactant [14] and in other challenging selective reductions, such as those of unsaturated aldehydes and ketones [28]. Llabres and co-workers [29] successfully showed the presence of Lewis acid centers in UiO-66 and used these Zr-based MOFs for the esterification of levulinic acid with various alcohols. The catalytically-active sites are coordination vacancies on the Zr-metal, arising from crystalline defects associated to linker deficiencies or from thermal dehydroxylation of the Zr-cluster [29,30]. Recently, a new range of Zr-MOFs has been reported, all based on the Zr6O4(OH)4(-CO2)n secondary building unit (SBU) and variously shaped carboxylic organic linkers [31]. One of these Zr-materials is MOF-808, in which the Zr-SBU is connected to six 1,3,5-benzenetricarboxylate (BTC) organic linkers and six formate ligands (Figure1a,b). Every linker is coordinated to three SBUs, resulting in tetrahedral and adamantane-shaped cages with an internal pore diameter of respectively 4.8 Å and 18 Å (Figure1c,d). These large pores are of interest for use of MOF-808 as MPV reduction catalyst since they might alleviate mass transport limitations and facilitate formation of the six-membered transition state. Furthermore, a new crystalline form of MOF-808—designated as MOF-808-P—has been described; it contains five instead of six formate ligands per cluster, resulting in Catalysts 2016, 6, 104 3 of 11 a coordinatively unsaturated Zr-site [32]. Citronellal cyclization experiments already indicated that CatalystsMOF-808-P 2016, 6 contains, 104 Lewis acid sites; such sites are suitable to catalyze MPV reduction [1]. 3 of 10

Figure 1. ((aa)) ZrZr66OO44(OH)4(HCOO)(HCOO)66(‐(-COCO2)26) 6metalmetal clusters, clusters, and and ( (bb)) 1,3,5 1,3,5-benzenetricarboxylate‐benzenetricarboxylate (BTC) (BTC) linkerslinkers form form (c ()c )tetrahedral tetrahedral cages cages (yellow (yellow spheres spheres represent represent the internal the internal free volume free volume inside inside these cages these withcages a withdiameter a diameter of 4.8 Å), of and 4.8 Å), (d) andlarge ( dadamantane) large adamantane-shaped‐shaped cages, internal cages, free internal volume free with volume diameter with ofdiameter 18 Å. Zr of coordination 18 Å. Zr coordination polyhedra, polyhedra, green; C: green;brown C: spheres; brown O: spheres; red spheres; O: red spheres;formate C formate and O: C half and‐ filled;O: half-ﬁlled; H omitted H omitted for clarity for (based clarity on (based Ref. on[31]). Ref. [31]).

InIn this work, MOF MOF-808-P‐808‐P is successfully used as MPV-catalystMPV‐catalyst forfor variousvarious αα,,ββ‐-unsaturatedunsaturated carbonyl compounds. For For cinnamaldehyde cinnamaldehyde and and citral, citral, allylic allylic alcohol alcohol yields yields of of respectively 99% and 95% were obtained within a very very short short reaction reaction time. time. More More challenging challenging substrates, substrates, such such as as RR‐-carvone,carvone, reached the equilibrium point, but this equilibrium could be shifted shifted towards towards the desired allyl alcohol by evaporation and the use of 1 1-Indanol.‐Indanol.

2. Results Results

2.1. Reduction Reduction of of Cinnamaldehyde and Carvone ZrZr-based‐based MOF MOF-808-P‐808‐P was was synthesized synthesized according according to the to thereported reported procedure, procedure, starting starting from from ZrOCl ¨ 8H O and 1,3,5-benzenetricarboxylic acid (BTC) dissolved in a mixture of ZrOCl2∙8H2O 2 and2 1,3,5‐benzenetricarboxylic acid (BTC) dissolved in a mixture of N,N‐ dimethylformamideN,N-dimethylformamide (DMF) (DMF) and andformic formic acid acid [32]. [32 In]. Incontrast contrast to to the the MOF MOF-808‐808 synthesis synthesis employing employing stoichiometric amounts of linkerlinker (ZrOCl(ZrOCl22/BTC = = 1/1) 1/1) [31], [31], MOF MOF-808-P‐808‐P is is synthesized synthesized with with an an excess of Zr Zr-source‐source (ZrOCl22/BTC = = 3/1), 3/1), resulting resulting in in formic formic acid acid ligand ligand deficiency deﬁciency and and an an increased increased number number of Lewis acid sites at the under under-coordinated‐coordinated Zr Zr-metal.‐metal. Characterization via powder X X-ray‐ray diffraction (XRD, see supporting Figure S1), scanning electron microscopy (SEM, see supporting Figure S2) and thermogravimetricthermogravimetric analysis analysis (TGA, (TGA, see see supporting supporting Figure Figure S3) S3) confirms conﬁrms that that the the correct structure is formedformed and that that it it crystallizes crystallizes in in octahedral octahedral microcrystals. Prior to to the the catalytic catalytic test, test, the the metal metal-organic‐organic ˝ frameworkframework (MOF) (MOF) is is activated at 150 °CC overnight to remove residual solvent molecules; at this temperature,temperature, activationactivation under under vacuum vacuum or or in in a regulara regular oven oven had had no effectno effect on the on resultingthe resulting powder powder XRD XRDnor on nor the on catalytic the catalytic activity. activity. ˝ Meerwein–Ponndorf–Verley (MPV)(MPV) reductionsreductions werewere carriedcarried outout at 120 °CC with isopropyl isopropyl alcohol alcohol (IPA) as as hydrogen hydrogen donor donor and and as solvent as solvent to move to move the equilibrium the equilibrium towards towards the desired the desired allylic alcohol allylic products.alcohol products. Catalytic Catalyticactivity of activity MOF‐808 of‐P MOF-808-P is compared is to compared UiO‐66 and to UiO-66 UiO‐66‐ andNO2 UiO-66-NO by keeping2 theby Zr/substratekeeping the ratio Zr/substrate constant ratio(Zr wt constant % is based (Zr on wt inductively % is based coupled on inductively plasma–atomic coupled emission plasma–atomic spectra (ICP–AES)emission spectra measurements (ICP–AES) and measurements theoretical structure and theoretical calculations; structure see supporting calculations; information see supporting and Table S1). Figure 2 shows that MOF‐808‐P is an excellent MPV‐catalyst with both high trans‐ cinnamaldehyde conversion (>99%) and high trans‐cinnamyl alcohol selectivity (>99%). Not only the yield is higher compared to the UiO‐66 materials; the reaction rate is considerably increased: after only 2 h, complete conversion with high selectivity is obtained. The outstanding catalytic

Catalysts 2016, 6, 104 4 of 11 information and Table S1). Figure2 shows that MOF-808-P is an excellent MPV-catalyst with both high trans-cinnamaldehyde conversion (>99%) and high trans-cinnamyl alcohol selectivity (>99%). Not only theCatalysts yield 2016 is, higher 6, 104 compared to the UiO-66 materials; the reaction rate is considerably increased:4 after of 10 only 2 h, complete conversion with high selectivity is obtained. The outstanding catalytic performance ofperformance MOF-808-P of is MOF even‐808 more‐P clearlyis even visiblemore clearly in the MPVvisible reduction in the MPV of R reduction-carvone inof FigureR‐carvone2b. After in Figure 2 h, 2b. After 2 h, the cis,trans‐carveol yield is 20‐fold higher than the yield obtained with UiO‐66 and the cis,trans-carveol yield is 20-fold higher than the yield obtained with UiO-66 and UiO-66-NO2 at theUiO same‐66‐NO time2 at in the the same same time reaction in the conditions. same reaction Even conditions. after reaction Even for after 24 h, reaction the UiO-66 for materials24 h, the UiO only‐ reach66 materials half of only the MOF-808-P reach half of yield the afterMOF 2‐808 h. ‐P yield after 2 h.

Figure 2.2. Meerwein–Ponndorf–Verley reduction of (a) transtrans-cinnamaldehyde‐cinnamaldehyde and (b) R-carvone‐carvone in isopropyl alcohol, catalyzed by Zr-basedZr‐based MOFs UiO-66-UiO‐66‐x and MOF-808-PMOF‐808‐P activated overnight at ˝ ˝ different temperatures: 150 °CC( (▲N)) andand 220220 °CC( (∆∆)) (a:(a: vacuumvacuum activation).activation). ( (c)) Hot ﬁltrationfiltration of thethe ˝ catalyst toto conﬁrmconfirm thatthat thethe catalysis catalysis is is truly truly heterogeneous. heterogeneous. (120 (120 C,°C, Zr/Substrate/IPA Zr/Substrate/IPA (Isopropyl alcohol) = 1/13/480, 250 250 rpm). rpm).

The increased activity activity of of MOF MOF-808-P‐808‐P can can be be partly partly attributed attributed to tothe the larger larger pores, pores, enhancing enhancing the theaccessibility accessibility of under of under-coordinated‐coordinated Zr‐ Zr-atomsatoms and and facilitating facilitating the the formation formation of of the six-memberedsix‐membered transition state, but more importantly to the Lewis acid sites on the under under-coordinated‐coordinated Zr Zr-atoms.‐atoms. Similar to mechanisms reported in literature [[1,3,33],1,3,33], a metal-alkoxidemetal‐alkoxide bond is formed with an isopropyl alcoholalcohol molecule molecule while while the the substrate substrate carbonyl-group carbonyl‐group is simultaneously is simultaneously activated activated via similar via coordinationsimilar coordination to a Zr-atom. to a BothZr‐atom. C-O bondsBoth C in‐O hydride bonds donorin hydride and acceptor donor and are in acceptor close proximity, are in close and hydrideproximity, transfer and occurshydride via transfer a six-membered occurs via transition a six‐ statemembered while maintainingtransition state stereochemistry. while maintaining Probing ofstereochemistry. the Lewis acid sitesProbing via sorptionof the Lewis with acid deuterated sites via acetonitrile sorption (CDwith3 CN)deuterated (Figure acetonitrile S4) indicated (CD a larger3CN) ratio(Figure of chemisorbedS4) indicated moleculesa larger ratio on Lewis of chemisorbed acid sites tomolecules physisorbed on Lewis molecules acid (vibrationsites to physisorbed frequency atmolecules 2297 cm (vibration´1 and 2265 frequency cm´1, at respectively) 2297 cm−1 and for 2265 MOF-808-P cm−1, respectively) compared for to MOF UiO-66‐808 after‐P compared activation to ˝ atUiO 150‐66 C.after Furthermore, activation at a large150 °C. fraction Furthermore, of the CD a 3largeCN molecules fraction of on the the CD Lewis3CN acidmolecules sites of on MOF-808-P the Lewis stayacid chemisorbedsites of MOF‐808 upon‐P stay desorption chemisorbed under upon vacuum desorption by increasing under temperature vacuum by increasing to 150 ˝C, temperature indicating a highto 150 acid °C, strength.indicating a high acid strength. It has often been observed that traces of DMF can be strongly adsorbed in the MOF structure, especially for for MOF MOF-808-P,‐808‐P, since since the the missing missing formate formate ligand ligand is most is most likely likely replaced replaced by a DMF by a or DMF water or watermolecule molecule [32]. ICP [32‐].AES ICP-AES indicates indicates a Zr weight a Zr weight percentage percentage of 39.4 of+/− 39.40.7 wt +/ ´%,0.7 a little wt %, lower a little than lower the thantheoretical the theoretical 40 wt % 40when wt % all when missing all missing linkers linkerswould be would replaced be replaced by water. by water.To investigate To investigate if some if someresidual residual DMF DMFmolecules molecules might might still be still adsorbed be adsorbed in the in MOF the MOF on the on thecatalytically catalytically active active sites sites as assuggested suggested by bythermogravimetric thermogravimetric analysis, analysis, the the activation activation temperature temperature was was increased increased from from 150 150 °C˝ toC to220 220 °C˝ Cunder under vacuum vacuum overnight. overnight. The The elevated elevated activation activation temperature temperature clearly clearly has has a detrimentaldetrimental impact on thethe catalyticcatalytic performance,performance, as as is is shown shown in in Figure Figure2 a.2a. Powder Powder X-ray X‐ray diffraction diffraction of of MOF-808-P MOF‐808‐ afterP after activation activation at at 220 220˝ C°C indicates indicates structure structure breakdown breakdown ofof thethe materialmaterial afterafter this activation step. step. Further experiments reported in this work were therefore always obtained with MOF‐808‐P catalyst activated at 150 °C. Leaching of Zr into the solution was investigated by hot filtration of the reaction mixture after 1 h to remove the catalyst. Filtrate conversion did not increase after 24 h, indicating that there is no leaching of catalytically‐active Zr into the solution, and the catalysis is truly heterogeneous (Figure 2c). The stability of MOF‐808‐P was retained upon activation and during the course of the reaction, as indicated by powder X‐ray diffraction (XRD) of recycled catalyst (supporting Figure S1). This

Catalysts 2016, 6, 104 5 of 11

Further experiments reported in this work were therefore always obtained with MOF-808-P catalyst activated at 150 ˝C. Leaching of Zr into the solution was investigated by hot ﬁltration of the reaction mixture after 1 h to remove the catalyst. Filtrate conversion did not increase after 24 h, indicating that there is no leaching of catalytically-active Zr into the solution, and the catalysis is truly heterogeneous (Figure2c).

CatalystsThe stability 2016, 6, of104 MOF-808-P was retained upon activation and during the course of the reaction,5 of as10 indicated by powder X-ray diffraction (XRD) of recycled catalyst (supporting Figure S1). This recycled recycledcatalyst is catalyst collected is collected via centrifugation via centrifugation after reaction after and reaction washed and with washed ethanol with and ethanol IPA four and times, IPA four after ˝ ˝ times,which after it was which activated it was ﬁrst activated at 60 C first and at overnight 60 °C and at overnight 150 C. Although at 150 °C. hot Although ﬁltration hot and filtration powder XRD and powderindicate XRD there indicate is no leaching there noris no perceptible leaching nor structure perceptible breakdown, structure activity breakdown, with the activity recycled with catalyst the recycleddrops by catalyst about 25% drops in theby about reduction 25% of in both the reduction cinnamaldehyde of both cinnamaldehyde and carvone. and carvone.

2.2. Increase Increase Equilibrium Equilibrium Carveol Yield InIn view of the remarkably short reaction time to reach the equilibrium point in the R‐-carvonecarvone reduction,reduction, this this specific speciﬁc reaction is further investigated to increase the yield. As As mentioned mentioned before, before, Meerwein–Ponndorf–Verley (MPV) (MPV) reduction reduction is is an an equilibrium reaction reaction with the reverse reaction called OppenauerOppenauer oxidation. oxidation. The Meerwein–Ponndorf–Verley–OppenauerThe Meerwein–Ponndorf–Verley–Oppenauer (MPVO) redox(MPVO) equilibrium redox equilibriumis determined is bydetermined the oxidation by the potentials oxidation of both potentials carbonyl–alcohol of both carbonyl–alcohol pairs. Aside from pairs. using Aside isopropyl from usingalcohol isopropyl as the solvent, alcohol two as otherthe solvent, strategies two can other be used strategies to shift can the be equilibrium used to shift towards the equilibrium the desired towardsproducts: the (1) desired distilling products: off acetone (1) distilling and (2) the off useacetone of stronger and (2) reducingthe use of alcohols. stronger Thereducing results alcohols. of both Thestrategies results are of shownboth strategies in Figure are3. shown in Figure 3.

Figure 3. ((aa)) Evaporation Evaporation of of acetone acetone and and isopropyl isopropyl alcohol alcohol (IPA) (IPA) and and addition addition of of fresh fresh IPA IPA solvent solvent ( (∆∆)) ˝ direct the equilibrium towardstowards aacis cis,trans,trans-carveol‐carveol yield yield of of 70% 70% (120 (120 C,°C, Zr/Substrate/IPA Zr/Substrate/IPA = = 1/13/480).1/13/480). (b) MPVMPV (Meerwein–Ponndorf–Verley) (Meerwein–Ponndorf–Verley) reduction reduction with with 12 equivalents 12 equivalents of strongly of strongly reducing reducing (S)-1-indanol (S)‐1‐ ˝ indanol(∆) drives (∆ the) equilibriumdrives the towardsequilibrium a cis ,transtowards-carveol a yieldcis,trans of 73%.‐carveol (120 yieldC, Zr/substrate/reducing of 73%. (120 °C, Zr/substrate/reducingagent/toluene = 1/13/156/480). agent/toluene = 1/13/156/480).

2.2.1. Evaporation Evaporation of of Acetone Acetone InIn the the first first strategy, two reactions are carried out simultaneously; one reaction is stopped after 2 h and both the solvent isopropyl alcohol and the formed acetone are removed by rotary vacuum evaporation. After After the the addition addition of offresh fresh isopropyl isopropyl alcohol, alcohol, carveol carveol yield yield reaches reaches 70% (Figure 70% (Figure 3a). This3a). isThis 20% is higher 20% higher than thanwithout without intermediate intermediate removal removal of acetone of acetone and and clearly clearly points points out out the the importance importance of theof the reverse reverse reaction, reaction, which which limits limits the the maximum maximum carveol carveol yield. yield. Based Based on on these these results, results, the the reaction was performedperformed under under reflux. reflux. Twenty Twenty mg ofmg activated of activated MOF-808-P MOF‐ together808‐P together with IPA, with internal IPA, standard,internal standard,and carvone and were carvone placed were in a 50placed mL two-mounted in a 50 mL two flask‐mounted connected flask to a connected condenser. to The a reactioncondenser. mixture The reaction mixture was refluxed at 80 °C and stirred at 250 rpm, while a N2‐flow was passed over the mixture to remove the formed acetone. The obtained yield after 4 h was comparable to the yield of the rotary evaporated sample (see supporting Figure S5). After 6 h, even 74% yield could be obtained; however, loss of isopropyl alcohol was also significant at that time, so the reaction could no longer proceed.

2.2.2. 1‐Indanol as Reducing Agent With the second strategy (the use of a stronger reducing alcohol [7,24]), the yield could be vastly increased to 73% (Figure 3b) with a diastereomeric excess (d.e.) for cis‐carveol of 90% (see supporting

Catalysts 2016, 6, 104 6 of 11

˝ was refluxed at 80 C and stirred at 250 rpm, while a N2-flow was passed over the mixture to remove the formed acetone. The obtained yield after 4 h was comparable to the yield of the rotary evaporated sample (see supporting Figure S5). After 6 h, even 74% yield could be obtained; however, loss of isopropyl alcohol was also significant at that time, so the reaction could no longer proceed.

2.2.2. 1-Indanol as Reducing Agent With the second strategy (the use of a stronger reducing alcohol [7,24]), the yield could be Catalysts 2016, 6, 104 6 of 10 vastly increased to 73% (Figure3b) with a diastereomeric excess (d.e.) for cis-carveol of 90% (see supporting information and supporting Figure S6). This reaction was carried out with information and supporting Figure S6). This reaction was carried out with 12 equivalents of (S)‐1‐ 12 equivalents of (S)-1-indanol in toluene as solvent. The reaction with 12 equivalents of isopropyl indanol in toluene as solvent. The reaction with 12 equivalents of isopropyl alcohol in toluene is also alcohol in toluene is also given as comparison in Figure3b. given as comparison in Figure 3b. 2.3. Substrate Scope 2.3. Substrate Scope Given the excellent catalytic performance of MOF-808-P both with trans-cinnamaldehyde and Given the excellent catalytic performance of MOF‐808‐P both with trans‐cinnamaldehyde and R‐ R-carvone, a series of other α,β-unsaturated aldehydes and ketones were tested. Figure4 shows that carvone, a series of other α,β‐unsaturated aldehydes and ketones were tested. Figure 4 shows that for the unsaturated aldehyde citral, high yields (>90%) are also obtained within a short time with high for the unsaturated aldehyde citral, high yields (>90%) are also obtained within a short time with selectivity (>98%). Furthermore, Figure4 shows that for the α,β-unsaturated ketones tested, complete high selectivity (>98%). Furthermore, Figure 4 shows that for the α,β‐unsaturated ketones tested, conversion is not reached; instead, an equilibrium is established. This equilibrium is influenced complete conversion is not reached; instead, an equilibrium is established. This equilibrium is by the redox potentials of the specific alcohol/ketone couples. We used isopropyl alcohol (IPA) as influenced by the redox potentials of the specific alcohol/ketone couples. We used isopropyl alcohol hydrogen donor and as solvent to shift the equilibrium towards the allylic alcohol product, but the (IPA) as hydrogen donor and as solvent to shift the equilibrium towards the allylic alcohol product, oxidation potential of these compounds is too low compared to that of the acetone/IPA couple to but the oxidation potential of these compounds is too low compared to that of the acetone/IPA couple allow complete conversion, as the reverse Oppenauer oxidation reaction takes place [6]. From the to allow complete conversion, as the reverse Oppenauer oxidation reaction takes place [6]. From the moment equilibrium is reached, selectivity starts to decrease due to the slow competing reactions that moment equilibrium is reached, selectivity starts to decrease due to the slow competing reactions continue to progress. Selectivity in favor of the allylic alcohol is high in all reactions, only in the case of that continue to progress. Selectivity in favor of the allylic alcohol is high in all reactions, only in the 4,4-dimethyl-2-cyclohexen-1-one, the saturated alcohol and etherification of the allylic alcohol with case of 4,4‐dimethyl‐2‐cyclohexen‐1‐one, the saturated alcohol and etherification of the allylic alcohol IPA are formed in significant amounts. with IPA are formed in significant amounts.

FigureFigure 4. Meerwein–Ponndorf–Verley4. Meerwein–Ponndorf–Verley (MPV) (MPV) reduction reduction of αof,β α-unsaturated,β‐unsaturated carbonyl carbonyl compounds compounds catalyzedcatalyzed by MOF-808-Pby MOF‐808 (120‐P (120˝C, Zr/Substrate/IPA°C, Zr/Substrate/IPA = 1/13/480, = 1/13/480, 250 250 rpm). rpm). Different Different colors colors indicate indicate samplingsampling at different at different reaction reaction times; times; dotted dotted bars bars represent represent conversion conversion at the at correspondingthe corresponding time time (X). (X).

3. Discussion From the broad substrate scope shown in Figure 4, it can be concluded that the cages and channels in MOF‐808‐P are sufficiently large to allow chemoselective transfer hydrogenation of bulky molecules like β‐ionone, with a yield of 77%. Aside from steric effects, electronic effects are also known to have an impact on the reactivity [6,7]. Electron donating substituents (such as methyl groups) increase the electron density of the carbonyl group, thereby reducing the hydrogen transfer, especially when present in the β‐position of the carbonyl group. This explains the relatively low yields for isophorone. Table 1 compares the allylic alcohol yields obtained with MOF‐808‐P, with the highest yields reported in literature for comparable catalyst systems. Compared to Zr‐zeolite Beta, that uses 1.3 mol % Zr to reach full conversion after 3 h, MOF‐808‐P obtained full cinnamaldehyde conversion within 2 h by using 7.7 mol % Zr (entry 1). For citral excellent allylic alcohol yield is also obtained within 4 h, in contrast to the Zr‐PhyA reported MPV‐catalyst that required 6 h to obtain 88% yield with a higher Zr mol % (150%) (entry 2). The reported yield for carvone and isophorone is

Catalysts 2016, 6, 104 7 of 11

3. Discussion From the broad substrate scope shown in Figure4, it can be concluded that the cages and channels in MOF-808-P are sufﬁciently large to allow chemoselective transfer hydrogenation of bulky molecules like β-ionone, with a yield of 77%. Aside from steric effects, electronic effects are also known to have an impact on the reactivity [6,7]. Electron donating substituents (such as methyl groups) increase the electron density of the carbonyl group, thereby reducing the hydrogen transfer, especially when present in the β-position of the carbonyl group. This explains the relatively low yields for isophorone. Table1 compares the allylic alcohol yields obtained with MOF-808-P, with the highest yields reported in literature for comparable catalyst systems. Compared to Zr-zeolite Beta, that uses 1.3 mol % Zr to reach full conversion after 3 h, MOF-808-P obtained full cinnamaldehyde conversion within 2 h by using 7.7 mol % Zr (entry 1). For citral excellent allylic alcohol yield is also obtained within 4 h, in CatalystsCatalysts 2016 2016, ,6 6, ,104 104 77 of of 10 10 Catalystscontrast 2016, to 6, the104 Zr-PhyA reported MPV-catalyst that required 6 h to obtain 88% yield with a7 higher of 10 Zr mol % (150%) (entry 2). The reported yield for carvone and isophorone is higher than the one higherhigher than than the the one one obtained obtained with with MOF MOF‐‐808808‐‐PP in in our our reaction reaction system system (entries (entries 3 3 and and 5); 5); however, however, the the higherobtained than with the one MOF-808-P obtained in with our MOF reaction‐808 system‐P in our (entries reaction 3 and system 5); however, (entries the3 and reactant 5); however, used in the these reactantreactant used used in in these these studies studies (1 (1‐‐indanol)indanol) is is more more strongly strongly reducing reducing than than the the isopropanol isopropanol used used in in this this reactantstudies used (1-indanol) in these isstudies more strongly(1‐indanol) reducing is more than strongly the isopropanol reducing than used the in isopropanol this work. Asused mentioned in this work.work. AsAs mentionedmentioned above,above, thethe obtainedobtained carveolcarveol yieldyield withwith indanolindanol andand MOFMOF‐‐808808‐‐PP surpassessurpasses thethe work.above, As thementioned obtained above, carveol the yield obtained with indanolcarveol yield and MOF-808-P with indanol surpasses and MOF the‐808 best‐P reportedsurpasses values the bestbest reportedreportedreported valuesvalues (Table(Table(Table 1,1, entryentry 3).3). ForFor comparison,comparison,comparison, aa homogeneoushomogeneous ZrZr‐‐‐catalyst—Zr(IV)catalyst—Zr(IV)catalyst—Zr(IV) acetylacetyl best(Table reported1, entry values 3). For (Table comparison, 1, entry 3). a homogeneous For comparison, Zr-catalyst—Zr(IV) a homogeneous Zr acetyl‐catalyst—Zr(IV) acetonate (Zr(acac) acetyl 4; acetonateacetonate (Zr(acac)(Zr(acac)44; ; obtainedobtained fromfrom ABCR,ABCR, AB122355)—wasAB122355)—was alsoalso testedtested underunder thethe samesame reactionreaction acetonateobtained (Zr(acac) from ABCR,4; obtained AB122355)—was from ABCR, also AB122355)—was tested under the also same tested reaction under conditions the same as MOF-808-P reaction conditionsconditions as as MOF MOF‐‐808808‐‐PP in in isopropyl isopropyl alcohol alcohol with with the the same same Zr Zr‐‐toto‐‐substratesubstrate ratio. ratio. After After 2 2 h h at at 120 120 °C, °C, conditionsin isopropyl as MOF alcohol‐808‐ withP in isopropyl the same alcohol Zr-to-substrate with the ratio. same Zr After‐to‐substrate 2 h at 120 ratio.˝C, very After little 2 h at conversion 120 °C, veryvery littlelittle conversionconversion waswas measured;measured; afterafter 2424 h,h, however,however, 62%62% ofof thethe initialinitial cinnamaldehydecinnamaldehyde waswas verywas little measured; conversion after was 24 h,measured; however, after 62% 24 of h, the however, initial cinnamaldehyde 62% of the initial was cinnamaldehyde converted with was 96% convertedconverted withwith 96%96% selectivityselectivity inin favorfavor ofof cinnamylcinnamyl alcohol.alcohol. ThisThis obtainedobtained cinnamylcinnamyl alcoholalcohol yieldyield convertedselectivity with in favor 96% selectivity of cinnamyl in alcohol. favor of This cinnamyl obtained alcohol. cinnamyl This alcohol obtained yield cinnamyl with the alcohol homogeneous yield withwith thethe homogeneoushomogeneous ZrZr‐‐catalystscatalysts isis stillstill 1.61.6 timestimes lowerlower thanthan forfor MOFMOF‐‐808808‐‐P,P, whilewhile reactionreaction timetime withZr-catalysts the homogeneous is still 1.6 Zr times‐catalysts lower is than still for 1.6 MOF-808-P, times lower while than reactionfor MOF time‐808‐ wasP, while 12 times reaction longer. time The waswas 12 12 times times longer. longer. The The same same activity activity trend trend is is observed observed in in the the MPV MPV reduction reduction of of carvone; carvone; after after 24 24 h h wassame 12 times activity longer. trend The is observedsame activity in the trend MPV is observed reduction in of the carvone; MPV reduction after 24 h of at carvone; 120 ˝C, after conversion 24 h 4 atat 120 120 °C, °C,°C, conversion conversionconversion reaches reachesreaches only only 7% 7% with with Zr(acac) Zr(acac)44.. . These These experiments experiments indicate indicateindicate heterogenization heterogenization of of at reaches120 °C, conversion only 7% with reaches Zr(acac) only4. 7% These with experiments Zr(acac)4. These indicate experiments heterogenization indicate heterogenization of Zr in the form of of a ZrZr inin thethe formform ofof aa porousporous catalyticallycatalytically‐‐activeactive materialmaterial isis notnot onlyonly beneficialbeneficial forfor itsits recyclability,recyclability, butbut Zrporous in the form catalytically-active of a porous catalytically material is‐active not only material beneﬁcial is not for only its recyclability, beneficial for but its also recyclability, for its activity. but alsoalso for for its its activity. activity. also for its activity. Table 1. Comparison of MOF-808-P obtained allylic alcohol yields with literature. TableTable 1. 1. Comparison Comparison of of MOF MOF‐‐808808‐‐PP obtained obtained allylic allylic alcohol alcohol yields yields with with literature. literature. Table 1. Comparison of MOF‐808‐P obtained allylic alcohol yields with literature. 2 1 1 Literature2 Entry Substrate t (h)tt YY 11 1 (%) SS 1S1 1 (%) LiteratureLiterature 2 2 EntryEntry SubstrateSubstrate t Y 1 S 1 Literature 2 Entry Substrate (h)(h) (%)(%) (%)(%) ConditionsConditionsConditions CatalystCatalyst Catalyst Ref.Ref. Ref. (h) (%) (%) Conditions Catalyst Ref.

transtrans‐‐ 96% 3 h, ZrZrZr-zeolite‐‐zeolitezeolite β β β 11 1 trans-cinnamaldehydetrans‐ 22 9999 99 9999 99 96%96% 3 3 h, h, IPA IPA Zr‐zeolite β [19][19][19] 1 cinnamaldehydecinnamaldehyde 2 99 99 96% 3 h,IPA IPA 1.31.31.3 mol mol mol % % Zr ZrZr [19] cinnamaldehyde 1.3 mol % Zr

88% 6 h, ZrZrZr-PhyA‐‐PhyAPhyA 22 2 cisciscis,trans,trans,trans‐‐-citralcitralcitral 44 9595 95 9898 98 88%88% 6 6 h, h, IPA IPA Zr‐PhyA [15][15][15] 2 cis,trans‐citral 4 95 98 88% 6 h,IPA IPA 150150150 mol mol mol % % ZrZr [15] 150 mol % Zr

62%62%62%62% 5 55 h, h, 5 h, ZrZrZr-MCM-41‐‐‐MCMMCM‐‐‐414141 33 3 RRR‐‐carvone-carvonecarvone 88 4848 48 9797 97 62% 5 h, Zr‐MCM‐41 [7][7][7 ] 3 R‐carvone 8 48 97 11‐‐indanolindanol1-indanol 55 5mol mol mol % % Zr ZrZr [7] 1‐indanol 5 mol % Zr

4,44,44,4‐‐‐dimethyldimethyl‐‐‐222‐‐‐ 4,44,4-dimethyl-2-‐dimethyl‐2‐ 44 cyclohexencyclohexen‐‐11‐‐ 2424 6060 8585 ‐ ‐ ‐ ‐ ‐ ‐ 4 4 cyclohexencyclohexen-1-‐1‐ 2424 60 6085 ‐ ‐ ‐ 85 - - - oneone oneone

40%40% 24 24 h, h, HfHf‐‐MCMMCM‐‐4141 55 isophoroneisophorone 4848 2424 7575 40% 24 h, Hf‐MCM‐41 [24][24] 5 isophorone 48 24 75 11‐‐indanolindanol 55 mol mol % % Hf Hf [24] 1‐indanol 5 mol % Hf

77%77% BB‐‐MCMMCM‐‐4141 66 β‐ β‐iononeionone 4848 7777 8989 77% B‐MCM‐41 [23][23] 6 β‐ionone 48 77 89 99 h, h, IPA IPA 44 mol mol % % B B [23] 9 h, IPA 4 mol % B

1 11 YieldYield andand selectivityselectivity areare givengiven forfor allylicallylic alcoholalcohol (120(120 °C,°C, Zr/Substrate/IPA Zr/Substrate/IPA == 1/13/480,1/13/480, 250250 rpm,rpm, 2020 1 Yield and selectivity are given for allylic alcohol (120 °C, Zr/Substrate/IPA = 1/13/480, 250 rpm, 20 2 mgmg catalyst);catalyst); 2 2 AllylicAllylic alcoholalcohol yield,yield, time,time, reducingreducing agent,agent, catalyst,catalyst, andand metalmetal molmol %% forfor thethe givengiven mg catalyst); 2 Allylic alcohol yield, time, reducing agent, catalyst, and metal mol % for the given references.references. references. 4. Materials and Methods 4.4. MaterialsMaterials andand MethodsMethods 4.1. Synthesis and Characterization 4.1.4.1. SynthesisSynthesis andand CharacterizationCharacterization All chemicals and solvents used in the syntheses were of reagent grade and used without further AllAll chemicalschemicals andand solventssolvents usedused inin thethe synthesessyntheses werewere ofof reagentreagent gradegrade andand usedused withoutwithout furtherfurther purification. purification.purification. 4.1.1. MOF Synthesis 4.1.1.4.1.1. MOFMOF SynthesisSynthesis The synthesis was performed according to the reported procedure. All materials were made in TheThe synthesissynthesis waswas performedperformed accordingaccording toto thethe reportedreported procedure.procedure. AllAll materialsmaterials werewere mademade inin a closed Schott DURAN® (VWR, Leuven, Belgium) pressure plus bottle with a volume of 1 L under aa closedclosed SchottSchott DURAN®DURAN® (VWR,(VWR, Leuven,Leuven, Belgium)Belgium) pressurepressure plusplus bottlebottle withwith aa volumevolume ofof 11 LL underunder staticstatic conditions conditions starting starting from from a a non non‐‐equimolarequimolar solution solution of of ZrOCl ZrOCl22∙8H∙8H22OO (9.7 (9.7 g, g, 30 30 mmol, mmol, 95%, 95%, ABCR ABCR static conditions starting from a non‐equimolar solution of ZrOCl2∙8H2O (9.7 g, 30 mmol, 95%, ABCR

Catalysts 2016, 6, 104 7 of 10 Catalysts 2016, 6, 104 7 of 10 higherhigher than than the the one one obtained obtained with with MOF MOF‐808‐808‐P ‐inP inour our reaction reaction system system (entries (entries 3 and3 and 5); 5); however, however, the the reactantreactant used used in inthese these studies studies (1 ‐(1indanol)‐indanol) is moreis more strongly strongly reducing reducing than than the the isopropanol isopropanol used used in inthis this work.work. As As mentioned mentioned above, above, the the obtained obtained carveol carveol yield yield with with indanol indanol and and MOF MOF‐808‐808‐P ‐surpassesP surpasses the the bestbest reported reported values values (Table (Table 1, 1,entry entry 3). 3). For For comparison, comparison, a homogeneousa homogeneous Zr Zr‐catalyst—Zr(IV)‐catalyst—Zr(IV) acetyl acetyl acetonate (Zr(acac)4; obtained from ABCR, AB122355)—was also tested under the same reaction acetonate (Zr(acac)4; obtained from ABCR, AB122355)—was also tested under the same reaction conditionsconditions as asMOF MOF‐808‐808‐P ‐inP inisopropyl isopropyl alcohol alcohol with with the the same same Zr Zr‐to‐‐tosubstrate‐substrate ratio. ratio. After After 2 h 2 ath at120 120 °C, °C, veryvery little little conversion conversion was was measured; measured; after after 24 24 h, h,however, however, 62% 62% of ofthe the initial initial cinnamaldehyde cinnamaldehyde was was convertedconverted with with 96% 96% selectivity selectivity in infavor favor of ofcinnamyl cinnamyl alcohol. alcohol. This This obtained obtained cinnamyl cinnamyl alcohol alcohol yield yield withwith the the homogeneous homogeneous Zr Zr‐catalysts‐catalysts is isstill still 1.6 1.6 times times lower lower than than for for MOF MOF‐808‐808‐P,‐ P,while while reaction reaction time time waswas 12 12 times times longer. longer. The The same same activity activity trend trend is isobserved observed in inthe the MPV MPV reduction reduction of ofcarvone; carvone; after after 24 24 h h at 120 °C, conversion reaches only 7% with Zr(acac)4. These experiments indicate heterogenization of at 120 °C, conversion reaches only 7% with Zr(acac)4. These experiments indicate heterogenization of ZrZr in inthe the form form of ofa porousa porous catalytically catalytically‐active‐active material material is isnot not only only beneficial beneficial for for its its recyclability, recyclability, but but also for its activity. also for its activity.

Table 1. Comparison of MOF‐808‐P obtained allylic alcohol yields with literature. Table 1. Comparison of MOF‐808‐P obtained allylic alcohol yields with literature. t Y 1 S 1 Literature 2 Entry Substrate t Y 1 S 1 Literature 2 Entry Substrate (h) (%) (%) Conditions Catalyst Ref. (h) (%) (%) Conditions Catalyst Ref. trans‐ Zr‐zeolite β 1 trans‐ 2 99 99 96% 3 h, IPA Zr‐zeolite β [19] 1 cinnamaldehyde 2 99 99 96% 3 h, IPA 1.3 mol % Zr [19] cinnamaldehyde 1.3 mol % Zr

Zr‐PhyA 2 cis,trans‐citral 4 95 98 88% 6 h, IPA Zr‐PhyA [15] 2 cis,trans‐citral 4 95 98 88% 6 h, IPA 150 mol % Zr [15] 150 mol % Zr

Catalysts 2016, 6, 104 62% 5 h, Zr‐MCM‐41 8 of 11 3 R‐carvone 8 48 97 62% 5 h, Zr‐MCM‐41 [7] 3 R‐carvone 8 48 97 1‐indanol 5 mol % Zr [7] 1‐indanol 5 mol % Zr Table 1. Cont. 4,4‐dimethyl‐2‐ 4,4‐dimethyl‐2‐ 4 cyclohexen‐1‐ 24 60 85 ‐ ‐ ‐ Literature 2 Entry4 cyclohexenSubstrate‐1‐ t (h)24 Y 160(%) S851 ‐ ‐ ‐ (%) one Conditions Catalyst Ref. one

40%40% 24 h, 24 h, HfHf-MCM-41‐MCM‐41 5 5isophorone isophorone 48 24 2475 75 40% 24 h, Hf‐MCM‐41 [24][24] 5 isophorone 48 24 75 1‐indanol1-indanol 5 5mol mol % % Hf Hf [24] 1‐indanol 5 mol % Hf

77% B‐MCM‐41 6 β‐ionone 48 77 89 77%77% B-MCM-41B‐MCM‐41 [23] 66 β‐β-iononeionone 4848 77 89 89 9 h, IPA 4 mol % B [23[23]] 9 9h, h, IPA IPA 44 mol mol % % B B 1 Yield and selectivity are given for allylic alcohol (120 °C, Zr/Substrate/IPA = 1/13/480, 250 rpm, 20 1 Yield1 Yield and and selectivity selectivity are givengiven for for allylic allylic alcohol alcohol (120 (120˝C, °C, Zr/Substrate/IPA Zr/Substrate/IPA = 1/13/480, = 1/13/480, 250 rpm,250 rpm, 20 mg 20 mg catalyst);2 2 Allylic alcohol yield, time, reducing agent, catalyst, and metal mol % for the given mgcatalyst); catalyst);Allylic 2 Allylic alcohol alcohol yield, time,yield, reducing time, reducing agent, catalyst, agent, and catalyst, metal mol and % formetal the givenmol % references. for the given references. references. 4. Materials and Methods 4. 4.Materials Materials and and Methods Methods 4.1. Synthesis and Characterization 4.1. Synthesis and Characterization 4.1. SynthesisAll chemicals and Characterization and solvents used in the syntheses were of reagent grade and used without furtherAllAll chemicals puriﬁcation. chemicals and and solvents solvents used used in inthe the syntheses syntheses were were of ofreagent reagent grade grade and and used used without without further further purification.purification. 4.1.1. MOF Synthesis 4.1.1. MOF Synthesis 4.1.1.The MOF synthesis Synthesis was performed according to the reported procedure. All materials were made in a closedTheThe synthesis Schottsynthesis DURAN was was performed performed®(VWR, according Leuven, according Belgium) to tothe the reported reported pressure procedure. procedure. plus bottle All All with materials materials a volume were were of made 1 made L under in in ¨ a closedastatic closed conditionsSchott Schott DURAN® DURAN® starting (VWR, from (VWR, a Leuven, non-equimolar Leuven, Belgium) Belgium) solution pressure pressure of ZrOCl plus plus bottle2 bottle8H2 withO with (9.7 a g, volumea 30volume mmol, of of1 95%, L1 underL under ABCR staticGmbH, conditions Karlsruhe, starting Germany) from a non and‐ 1,3,5-benzenetricarboxylicequimolar solution of ZrOCl acid2∙8H (BTC)2O (9.7 (2.1 g, g,30 10mmol, mmol, 95%, 98%, ABCR ABCR static conditions starting from a non‐equimolar solution of ZrOCl2∙8H2O (9.7 g, 30 mmol, 95%, ABCR GmbH, Karlsruhe, Germany) dissolved in a mixture of N,N-dimethylformamide (DMF) (450 mL, 6 mol,

>99%, Acros Organics, Geel, Belgium) and formic acid (450 mL, 12 mol, >98%, Acros Organics, Geel, Belgium). The synthesis mixture was placed in a preheated oven at 120 ˝C for 48 h. The powder was collected via centrifugation (10 min, 11 000 rpm) and thoroughly washed with DMF (3 times/day for 3 days) and methanol (HPLC grade, Chem-Lab Analytical BVBA, Zedelgem, Belgium) (3 times/day for 3 days). Finally, the material was activated at 150 ˝C in air to remove residual solvent molecules.

4.1.2. MOF Characterization Powder X-ray diffractograms were routinely collected on a STOE STADI COMBI P diffractometer (STOE & Cie GmbH, Darmstadt, Germany) in High-Throughput mode, equipped with an image plate detector using Cu Kα radiation (λ = 1.54056 Å). Scanning Electron Microscopy (SEM) images were obtained using a JEOL SEM (JSM-6010LV, Jeol Europe BV, Zaventem, Belgium). MOF-808-P was analyzed by Thermogravimetric Analysis (TGA) under a stream of O2-gas using a Universal V4.5A TA Instrument (TA Instruments, New Castle, DE, USA). CD3CN chemisorption spectra were measured on a Nicolett 6700 (Thermo Scientiﬁc, Waltham, MA, USA) FTIR (128 scans, resolution of 2 cm´1) and analyzed with Omnic software (Version 8.0, Thermo Scientiﬁc). Inductively Coupled Plasma (ICP)—Atomic Emission Spectra (AES) were recorded on a Varian 720-ES (Varian Inc., Walnut Creek, CA, USA).

4.2. Catalytic Experiments Before reaction, each catalyst was dried at 150 ˝C for 16 h to remove residual solvent molecules. Catalytic reactions were carried out in 10 mL glass crimp cap vials loaded with 20–30 mg catalyst and a magnetic stirring bar. A solution of the substrate in 3.3 mL isopropyl alcohol (IPA) (extra pure, Acros Organics, Geel, Belgium) was added; tetradecane (99%, TCI Europe NV, Zwijndrecht, Belgium) was added as internal standard. For each catalyst and substrate, a substrate-to-Zr ratio of 7.8 was used to Catalysts 2016, 6, 104 9 of 11 compare the activity of each catalyst for every substrate. After introduction of the reaction mixture, the vials were placed in an aluminum heating block (at 120 ˝C) and stirred (250 rpm). Reaction samples were filtered through a 0.45 µm PTFE filter (Thermo scientific, VWR, Leuven, Belgium) and analyzed with a Shimadzu 2010 GC (Shimadzu Benelux BV, Brussel, Belgium) equipped with a CP-Sil 8 column and a FID detector. Reaction products were identified using GC-MS (Agilent Technologies Belgium, Diegem, Belgium).

5. Conclusions The Zr-based MOF-808-P was successfully used as a Meerwein–Ponndorf–Verley reduction catalyst for various α,β-unsaturated aldehydes and ketones. For typical substrates such as trans-cinnamaldehyde and cis,trans-citral, yields of respectively 99% and 95% were obtained within a short reaction time. Because of the increased number and strength of Lewis acid sites on coordinatively unsaturated Zr-atoms, the cis,trans-carveol yield increased 20-fold compared to reactions using another Zr-based MOF, UiO-66. For more challenging substrates, the equilibrium and reverse reduction of acetone prevented complete conversion. Two strategies were successfully used to shift the equilibrium towards the desired allylic alcohol products: evaporation of formed acetone and the use of the more strongly reducing 1-indanol increased the cis,trans-carveol yield from 50% to more than 70%.

Supplementary Materials: The following are available online at www.mdpi.com/2073-4344/6/7/104/s1, Figure S1: Powder X-ray diffractograms of MOF-808-P: simulated MOF-808 pattern, as synthesized MOF-808-P, activated at 150 ˝C and 200 ˝C for 16 h and recycled after reaction. Figure S2: SEM micrograph of MOF-808-P. Figure S3: Thermogravimetric Analysis. Figure S4: Normalized FTIR spectra of CD3CN chemisorption on MOF-808-P (a) and UiO-66 (b) at 10 mbar (RT) and desorption under vacuum at increasing temperature. Figure S5: Evaporation of acetone and isopropanol and addition of fresh IPA solvent (˝) indicate that the equilibrium of the Meerwein–Ponndorf–Verley (MPV) reduction of R-carvone with MOF-808-P can be shifted towards cis,trans-carveol. By performing the reaction under reflux at 80 to 100 ˝C, yield could be increased to 74%. Figure S6: MPV reduction of R-carvone with MOF-808-P with 5 (filled) or 12 (open) equivalents of (S)-1-Indanol. When yield of cis,trans-carveol (,˝) reaches equilibrium (73%), epimerization occurs and the diastereomeric excess (d.e., , ) decreases. (120 ˝C, Zr/substrate/reducing agent/toluene = 1/13/156/480). Table S1: Theoretical molecular formula# and Zr-percentage compared to ICP-AES analysis of self-synthesized MOF-808-P activated at 150 ˝C (16 h). Acknowledgments: The authors thank the Research Foundation-Flanders (FWO) (PhD scholarship to E.P.), the China Scholarship Council (PhD scholarship to G.F.), the European Union (Horizon 2020) and the Marie Sklodowska-Curie innovation program (Grant 641887 for PhD scholarship to C.Y.X.T.) and Belspo (IAP-VII/05) for financial support. Author Contributions: M.B.J.R. and D.E.D.V. conceived the project; E.P. performed the catalytic experiments, analyzed the data and wrote the paper; G.F. synthesized and characterized the materials via SEM and TGA; C.Y.X.T. performed CD3CN chemisorption measurements. Conflicts of Interest: The authors declare no conflict of interest.

Abbreviations The following abbreviations are used in this manuscript: BTC 1.3.5-benzenetricarboxylic acid IPA Isopropyl alcohol MOF Metal-Organic Framework MPV Meerwein–Ponndorf–Verley XRD X-ray diffraction

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