Metathesis of Functionalized Alkane: Understanding the Unsolved Story

catalysts

Communication Metathesis of Functionalized Alkane: Understanding the Unsolved Story

Mykyta Tretiakov, Yury Lebedev, Manoja K. Samantaray *, Aya Saidi , Magnus Rueping * and Jean-Marie Basset * KAUST Catalysis Center (KCC), King Abdullah University of Science & Technology, Thuwal 23955-6900, Saudi Arabia; [email protected] (M.T.); [email protected] (Y.L.); [email protected] (A.S.) * Correspondence: [email protected] (M.K.S.); [email protected] (M.R.); [email protected] (J.-M.B.)

Received: 6 February 2019; Accepted: 23 February 2019; Published: 4 March 2019

Abstract: For the ﬁrst time, we developed a method which enables a functionalized alkane to be metathesized to its lower and higher homologues. For this metathesis reaction, we used [(≡Si-O-)W(CH3)5] as a catalyst precursor and 9-hexyl-9H-carbazole as a reactant.

Keywords: metathesis; functionalized alkane; tungsten; carbazole; reaction mechanism; pyrrole

1. Introduction Since the discovery of alkane metathesis reaction by well-defined silica supported [Ta]-H catalyst [1], many groups, including us, have been continuously working on the development of well-defined catalysts for “functionalized” alkanes metathesis reaction or alkyl chains bearing any functionality, along with improved reactivity in alkane metathesis reaction [2–8]. While significant progress was achieved in improving the catalyst activity (e.g., by changing catalyst support and by employing a tandem system, where two catalysts act back to back for cascade reaction), metathesis of a functionalized alkane remains elusive in the scientific community [7,9–12]. To metathesize a functionalized alkane, the reactant should undergo dehydrogenation to a functionalized olefin, functionalized olefin metathesis, and finally reduction of the newly-formed, functionalized olefins to new functionalized alkanes. The main difficulty in functionalized alkane metathesis reaction is the functional moiety, which is expected to poison the catalyst by coordinating with the metal, and hence deactivating the system for further reaction. Therefore, it is a tremendous challenge to metathesize an alkane having a functional group. Herein we present the first example of functionalized alkane metathesis using silica supported W(CH3)5 1 as a catalyst precursor and 9-Hexyl-9H-carbazole 6 as a reactant.

2. Results and Discussion From previous publications it was known that ligands that have a lone pair of electrons coordinate with electron-deficient early-transition metals, making them electron-rich and blocking the coordination site for C-H bond activation [13]. As the metal is more electron-rich and coordinatively more saturated, its affinity towards alkane decreases [14]. Considering, that alkane metathesis occurs first by sigma-bond metathesis with a d0 system, this becomes increasingly important [15]. To avoid this problem, while carrying out the functionalized alkane metathesis reaction, our first aim was to focus on the protection of the functional group. To implement this idea, we chose N-Alkyl pyrroles, with the assumption that the lone pair of electrons on the nitrogen atom is involved in the formation of an aromatic system and thus is poorly available for coordination. To our surprise, after many attempts, we only observed a starting material along with its decomposition products.

Catalysts 2019, 9, 238; doi:10.3390/catal9030238 www.mdpi.com/journal/catalysts Catalysts 2019, 9, 238 2 of 10 Catalysts 2019, 9, 238 2 of 10 manyCatalysts attempts,2019, 9 , 238we only observed a starting material along with its decomposition products.2 of 10 A manyliterature attempts, report showswe only that observed pyrroles ainteract starting with ma Lewisterial alongacids towith produce its decomposition pyrrole oligomers products. through A literature report shows that pyrroles interact with Lewis acids to produce pyrrole oligomers through the activationA literature of report its α showsposition that [16]. pyrroles To avoid interact this, with and Lewis to carry acids out to produce the reaction, pyrrole we oligomers thought through to protect the activation of its α position [16]. To avoid this, and to carry out the reaction, we thought to protect the mostthe activation reactive of α its positionα position of[ 16the]. Topyrrole avoid this,ring and by tometh carryyl out groups, the reaction, in order we thoughtto avoid to protectunwanted thereactions mostthe most reactiveof reactivethe pyrroleαα positionposition ring ofof thewhile the pyrrole pyrrole carrying ring ring by ou methyl byt the meth groups, metathesis.yl groups, in order We toin avoid ordersynthesized unwanted to avoid reactions1-Hexyl-2,5- unwanted reactionsDimethyl-1H-pyrroleof the pyrroleof the ringpyrrole while 2 and ring carrying 1-Propyl-2,5-Dimethyl-1H-pyrrole while out thecarrying metathesis. out Wethe synthesized metathesis. 3 [17,18] 1-Hexyl-2,5-Dimethyl-1 We (Scheme synthesized 1) and H1-Hexyl-2,5- -pyrrolecarried out Dimethyl-1H-pyrrole 2 and 1-Propyl-2,5-Dimethyl-1H-pyrrole 3 [17,18] (Scheme 1) and carried out the metathesis2 and 1-Propyl-2,5-Dimethyl-1 reaction using [(≡HSi-O-)W(CH-pyrrole 3 [173),518] 1] (Schemeas a catalyst1) and precursor carried out (Figure the metathesis 1). reaction the metathesisusing [(≡Si-O-)W(CH reaction using3)5] 1 [(as≡ aSi-O-)W(CH catalyst precursor3)5] 1 as (Figure a catalyst1). precursor (Figure 1).

Figure 1. Well-defined silica-supported [(≡Si-O-)W(CH3)5] 1. Figure 1. Well-deﬁned silica-supported [(≡Si-O-)W(CH3)5] 1. Figure 1. Well-defined silica-supported [(≡Si-O-)W(CH3)5] 1.

Scheme 1. Synthesis of N-Alkyl pyrroles. Scheme 1. Synthesis of N-Alkyl pyrroles. Scheme 1. Synthesis of N-Alkyl pyrroles. It has been already observed that 1 leads to [(≡Si-O-)W(H)3(=CH2)] during catalyst activation [19]. WhileIt has testingbeen already this family observed of molecules, that 1 leads expecting to [( the≡Si-O-)W(H) metathesis3(=CH products2)] during of the reactants catalyst 2activationand 3, we [19]. WhileendedIt testinghas been up this with already family unreacted observed of molecules, starting that material 1 expect leads along ingto [( the≡ withSi-O-)W(H) metathesis traces of3(=CH decomposition, products2)] during of the andcatalyst reactants isomerization activation 2 and of 3 [19]., we Whileendedboth testingup the with substrates this unreacted family without of starting molecules, any metathesismaterial expect along product.ing the with metathesis traces of decomposition,products of the reactantsand isomerization 2 and 3, we of endedboth the up substratesThe with alkane unreacted without metathesis starting any consists metathesis material of mainly alongproduct. threewith traces subsequent of decomposition, paths—dehydrogenation, and isomerization olefin of both metathesis,Thethe substratesalkane and metathesis without hydrogenation—as any consists metathesis weof mainly did product. not observethree subsequent any expected paths—dehydrogenation, metathesis products from the olefin above two reactants, we decided to investigate if the olefin metathesis step could be performed in our metathesis,The alkane and hydrogenation—asmetathesis consists we of didmainly not obsethreerve subsequent any expected paths—dehydrogenation, metathesis products from olefin the catalytic system. We synthesized 1-Allyl-2,5-Dimethyl-1H-pyrrole 4, which is the olefinic analogue of metathesis,above two reactants,and hydrogenation—as we decided to weinvestigate did not obseif therve olefin any expectedmetathesis metathesis step could products be performed from the in abovethe two 1-Propyl-2,5-Dimethyl-1 reactants, we decidedH-pyrrole to investigate2, for olefin if metathesisthe olefin reactionmetathesis using step catalyst could1 (Figure be performed2). in our catalyticThe productsystem. was We analyzed synthesized by gas 1-Allyl-2,5-Dimethyl-1H-pyrrole chromatography (GC), gas chromatography 4, which coupled is the witholefinic our catalytic system. We synthesized 1-Allyl-2,5-Dimethyl-1H-pyrrole 4, which is the olefinic analoguemass spectrometryof the 1-Propyl (GC-MS),-2,5-Dimethyl-1H-pyrrole and nuclear magnetic 2, resonance for olefin (NMR) metathesis spectroscopy, reaction confirming using catalyst the 1 analogue of the 1-Propyl-2,5-Dimethyl-1H-pyrrole 2, for olefin metathesis reaction using catalyst 1 (Figureformation 2). of expected product 1,4-bis-(2,5-Dimethyl-1H-pyrrole-1yl)but-2-ene, with 85% conversion (Figure 2). and a turnover number (TON) of 850 (Figure2)[ 20–22]. These results clearly indicated that our catalyst was capable of carrying out the olefin metathesis reaction for this particular substrate, whereas in the case of 1-Propyl-2,5-Dimethyl-1H-pyrrole 2 or 1-Hexyl-2,5-Dimethyl-1H-pyrrole 3, no metathesis was observed. The limiting step in the latter case was the alkyl chain C-H activation (as an entry into the alkane metathesis productive cycle). During the catalytic reaction, we understood that isomerization of the substrates occurs because of walking of α-methyl groups on the ring [23]. To avoid that, we thought to synthesize 9-Hexyl-9H-carbazole (a rigid molecule) to carry out the metathesis reaction. 9-Hexyl-9H-carbazole was obtained by the reaction of carbazole and hexyl bromide in the presence of KOH, by following a literature procedure (Scheme2)[24].

Catalysts 2019, 9, 238 3 of 10

100

40 Conversion (%) 30

0 Catalysts 2019, 9, 238 0 20406080100120 3 of 10 Catalysts 2019, 9, 238 Time (h) 3 of 10

100 Figure 2. Metathesis of 1-Alkyl-2,5-Dimethyl-1H-pyrrole, conversion versus time plot. ( ) Reaction CatalystsCatalysts 20192019,, 99,, 238238 90 33 ofof 1010 at room temperature (RT); ( ) reaction at 150 °C. 80 100100

9090 The product was analyzed70 by gas chromatography (GC), gas chromatography coupled with 8080 mass spectrometry (GC-MS),60 and nuclear magnetic resonance (NMR) spectroscopy, confirming the 7070 formation of expected product 1,4-bis-(2,5-Dimethyl-1H-pyrrole-1yl)but-2-ene, with 85% conversion 50 6060 and a turnover number (TON) of 850 (Figure 2) [20–22]. These results clearly indicated that our 40 5050

catalyst was capable Conversion (%) of carrying4040 out the olefin metathesis reaction for this particular substrate, Conversion (%) 30 Conversion (%) whereas in the case of 1-Propyl-2,5-Dimethyl-1H-pyrrole3030 2 or 1-Hexyl-2,5-Dimethyl-1H-pyrrole 3, no 20 metathesis was observed. The2020 limiting step in the latter case was the alkyl chain C-H activation (as an entry into the alkane10 metathesis1010 productive cycle). During the catalytic reaction, we understood 00 that isomerization of the0 substrat00es 20406080100120occurs 20406080100120 because of walking of α-methyl groups on the ring [23]. To avoid that, we thought0 to synt 20406080100120hesize 9-Hexyl-9H-carbazoleTimeTime (h)(h) (a rigid molecule) to carry out the Time (h) metathesis reaction. 9-Hexyl-9H-carbazole was obtained by the reaction of carbazole and hexyl bromide inFigureFigure theFigure presence 2.2. Metathesis 2.MetathesisMetathesis of ofof KOH, of 1-Alkyl-2,5-Dimethyl-1H-pyrrole,1-Alkyl-2,5-Dimethyl-1H-pyrrole, 1-Alkyl-2,5-Dimethyl-1 by following Ha -pyrrole,literature conversionconversion conversion procedure versusversus versus timetime (Scheme plot.plot ( )2)) .ReactionReaction ( [24].) at atat roomroom temperaturetemperature (RT);(RT); ( ) reactionreaction atat 150150 °C.◦°C. Figure 2. Metathesisroom temperature of 1-Alkyl-2,5-Dimethyl-1H-pyrrole, (RT); ( ) reaction( at 150 C. conversion versus time plot. ( ) Reaction Hexyl Bromide at room temperatureTheThe productproduct (RT);waswas analyzedanalyzed ( ) reaction byby gasgas at chromatographychromatography 150 °C. (GC),(GC), gasgas chromatographychromatography coupledcoupled withwith KOH massmass spectrometryspectrometry (GC-MS),(GC-MS), andand nuclearnuclear magneticmagneticDMF resonanceresonance (NMR)(NMR) spectroscopy,spectroscopy, confirmingconfirming thethe formationformation ofof expectedexpected productproduct 1,4-bis-(2,5-Dimethyl-1H-pyrrole-1yl)but-2-ene,1,4-bis-(2,5-Dimethyl-1H-pyrrole-1yl)but-2-ene, withwith 85%85% conversionconversion The product was analyzed by gas chromatographyRT, 9h (GC), gas chromatography coupled with andand aa turnoverturnover numbernumber (TON)(TON) ofofN 850850 (Figure(Figure 2)2) [20–22].[20–22]. TheseThese resultsresultsN clearlyclearly indicatedindicated thatthat ourour H 1 mass spectrometrycatalystcatalyst waswas (GC-MS), capablecapable ofof carryingcarryingand nuclear outout thethe magnetic olefinolefin metameta thesisresonancethesis reactionreaction (NMR) forfor2 thisthis spectroscopy,particularparticular substrate,substrate, confirming the formation whereasof expected in the case product of 1-Propyl-2,5-Dimethyl-1H-pyrrole 1,4-bis-(2,5-Dimethyl-1H-pyrrole-1yl)but-2-ene,2 or 1-Hexyl-2,5-Dimethyl-1H-pyrrole3 with3, 85% no conversion whereas in the case of 1-Propyl-2,5-Dimethyl-1H-pyrrole5 2 or 1-Hexyl-2,5-Dimethyl-1H-pyrrole6 4 3, no and a turnovermetathesismetathesis number waswas observed.observed. (TON) The The of limitinglimiting 850 (Figure stepstep inin thethe 2) latterlatter [20–22]. casecase waswas These thethe alkylalkyl results chainchain C-H C-Hclearly activationactivation indicated (as(as that our an entry into the alkane metathesis productive cycle). During the catalytic5 reaction,6 we understood catalyst wasan entrycapable into the of alkane carrying metathesis out productive the olefin cycle). meta Duringthesis the catalyticreaction reaction, for this we understood particular substrate, thatthat isomerizationisomerization ofof thethe substratsubstratSchemeeses occursoccurs 2. Synthesis becausebecause of of 9-Hexyl-9of walkingwalkingH-carbazole ofof αα-methyl-methyl6. groupsgroups onon thethe ringring [23].[23]. Scheme 2. Synthesis of 9-Hexyl-9H-carbazole 6. whereas inToTo the avoidavoid case that,that, of wewe1-Propyl-2,5-Dimethyl-1H-pyrrole thoughtthought toto syntsynthesizehesize 9-Hexyl-9H-carbazole9-Hexyl-9H-carbazole 2 or (a(a 1-Hexyl-2,5-Dimethyl-1H-pyrrole rigidrigid molecule)molecule) toto carrycarry outout thethe 3, no metathesismetathesismetathesis was Inobserved. a typicalreaction.reaction. reaction, The9-Hexyl-9H-carbazole9-Hexyl-9H-carbazole limiting 9-Hexyl-9H step-carbazole wasinwas the obob6 andtained tainedlatter [(≡ Si-O-)W(CHbyby case thethe reactionwasreaction3 )the5] 1ofof, inalkyl carbazolecarbazole 50:1 molarchain andand ratio, C-H hexylhexyl based activation (as Inbromidebromide aon typical loading inin thethereaction, of presencepresence W, were 9-Hexyl-9H-carbazole ofof mixed. KOH,KOH, byby The followifollowi mixturengng aa wasliteratureliterature 6 and sealed [( procedureprocedure≡ inSi-O-)W(CH an ampoule (Scheme(Scheme3) tube5 ]2)2) 1, [24].[24]. underin 50:1 high molar vacuum ratio, based an entry into the alkane metathesis productive◦ cycle). During the catalytic reaction, we understood on loadingand of the W, reaction were continuedmixed. The at 150mixtureC. The was first sealed sample in was an quenched ampoule with tube dichloromethane under high vacuum and and that isomerizationinjected inof GC the after substrat one dayes of reaction.occurs ToHexylHexylbecause our Bromide Bromide surprise, of walking neither any of considerable α-methyl amount groups of product on the ring [23]. the reaction continued at 150 °C. The first sampleKOHKOH was quenched with dichloromethane and injected nor decomposition of the starting material (9-Hexyl-9H-carbazole) were observed. We continued To avoidin GC that,after weone thoughtday of reaction. to synt hesizeTo our 9-Hexyl-9H-carbazolesurpriseDMFDMF , neither any cons (aiderable rigid molecule) amount of to product carry outnor the the reaction for another four days. After five days, the reaction mixture was taken, quenched with metathesis reaction. 9-Hexyl-9H-carbazoleNN wasRT,RT, 9h 9hobtainedN Nby the reaction of carbazole and hexyl decompositiondichloromethane, of the starting filtered, andmaterial analyzedHH (9-Hexyl by GC.-9H-carbazole) We could observe were a range observed. of alkylated We carbazoles, continued the 11 22 bromidereaction in thestartingfor presenceanother from cC 2 fourofto cCKOH, days.10, with by After a conversionfollowi fiveng days, of a starting literature the material reaction procedure of33 2.5% mixture and the(Scheme was formation taken, 2) of [24]. carbazolequenched with 55 66 44 dichloromethane,itself (Figures filtered,3 and4). and While analyzed carrying outby theGC. reaction We could with observe1, we thought a range the reactionof alkylated would carbazoles, go smoother, as the lone pair was delocalizedHexyl in Bromide the carbazole conjugated55 66 system and there was no starting from cC2 to cC10, with a conversion of starting material of 2.5% and the formation of carbazole labile group on the ring. To our surprise, weKOH only obtained 5.0% conversion, even after 30 days. itself (Figures 3 and 4). WhileScheme Schemecarrying 2.2.SynthesisSynthesis out the ofof 9-Hexyl-9H-carbazole9-Hexyl-9H-carbazolereaction with 1, 6.6.we thought the reaction would go While analyzing the reaction mixture, we observedDMF linear alkanes (alkane metathesis products), smoother,N-Alkyl as the carbazoles lone pair and was the delocalized dimer of 9-Hexyl-9 in theRT,H-carbazole carbazole 9h (functionalized conjugated alkanesystem metathesis and there products) was no labile InIn aa typicaltypical reaction,reaction, 9-Hexyl-9H-carbazole9-Hexyl-9H-carbazoleN 66 andand [([(≡≡Si-O-)W(CHSi-O-)W(CHN33))55]] 1,1, inin 50:150:1 molarmolar ratio,ratio, basedbased group on(Figures the ring.3 and To4; Supplementaryour surpriseH , Materialwe only Figures obtained S15–S17), 5.0% along conver withsion, a considerable even after amount 30 days. While onon loadingloading ofof W,W, werewere mixed.mixed. TheThe mixturemixture waswas sealed sealed inin an an ampoule ampoule1 tubetube2 underunder highhigh vacuumvacuum andand theof reaction carbazole. continued at 150 °C. The first sample was quenched with dichloromethane and injected analyzingthe reaction the reaction continued mixture, at 150 °C. we The observed first sample linear was quenched alkanes with(alkane dichloromethane3 metathesis and products), injected N-Alkyl carbazolesinin GCGC and afterafter onetheone daydaydimer ofof reaction.reaction. of 9-Hexyl-9H-carbazole5 ToTo ourour surprisesurprise,, neitherneither (functionalized anyany conscons6iderableiderable4 amountamountalkane of ofmetathesis productproduct nornor products) decompositiondecomposition ofof thethe startingstarting materialmaterial (9-Hexyl (9-Hexyl-9H-carbazole)-9H-carbazole) werewere observed.observed. WeWe continuedcontinued thethe 5 6 reactionreaction forfor another another fourfour days.days. AfterAfter fivefive days,days, thethe reactionreaction mixturemixture waswas taken,taken, quenchedquenched withwith

dichloromethane,dichloromethane, filtered,filtered, andand analyzedanalyzed byby GC.GC. WeWe couldcould observeobserve aa rangerange ofof alkylatedalkylated carbazoles,carbazoles, Scheme 2. Synthesis of 9-Hexyl-9H-carbazole 6. startingstarting fromfrom cCcC22 toto cCcC1010,, withwith aa conversionconversion ofof startingstarting materialmaterial ofof 2.5%2.5% andand thethe formationformation ofof carbazolecarbazole itselfitself (Figures(Figures 33 andand 4).4). WhileWhile carryingcarrying outout thethe reactionreaction withwith 11,, wewe thoughtthought thethe reactionreaction wouldwould gogo In a typicalsmoother,smoother, reaction, asas thethe lonelone 9-Hexyl-9H-carbazole pairpair was was delocalizeddelocalized inin thethe carbazolecarbazole 6 and [( conjugatedconjugated≡Si-O-)W(CH systemsystem 3 andand)5] 1,therethere in waswas50:1 nono molar labilelabile ratio, based on loadinggroupgroup of W, onon werethethe ring.ring. mixed. ToTo ourour The surprisesurprise mixture,, wewe onlyonly was obtainedobtained sealed 5.0%5.0% in converconveran ampoulesion,sion, eveneven tube afterafter 3030under days.days. highWhileWhile vacuum and analyzing the reaction mixture, we observed linear alkanes (alkane metathesis products), N-Alkyl the reactionanalyzing continued the reaction at 150 mixture, °C. The we first observed sample linear was alkanes quenched (alkane metathesis with dichloromethane products), N-Alkyl and injected carbazolescarbazoles andand thethe dimerdimer ofof 9-Hexyl-9H-carbazole9-Hexyl-9H-carbazole (functionalized(functionalized alkanealkane metathesismetathesis products)products) in GC after one day of reaction. To our surprise, neither any considerable amount of product nor decomposition of the starting material (9-Hexyl-9H-carbazole) were observed. We continued the reaction for another four days. After five days, the reaction mixture was taken, quenched with dichloromethane, filtered, and analyzed by GC. We could observe a range of alkylated carbazoles, starting from cC2 to cC10, with a conversion of starting material of 2.5% and the formation of carbazole itself (Figures 3 and 4). While carrying out the reaction with 1, we thought the reaction would go smoother, as the lone pair was delocalized in the carbazole conjugated system and there was no labile group on the ring. To our surprise, we only obtained 5.0% conversion, even after 30 days. While analyzing the reaction mixture, we observed linear alkanes (alkane metathesis products), N-Alkyl carbazoles and the dimer of 9-Hexyl-9H-carbazole (functionalized alkane metathesis products)

Catalysts 2019, 9, 238 4 of 10 Catalysts 2019, 9, 238 4 of 10 (Figures 3 and 4; Supplementary Material Figures S15–17), along with a considerable amount of (Figurescarbazole. 3 and 4; Supplementary Material Figures S15–17), along with a considerable amount of carbazole. Catalysts 2019, 9, 238 4 of 10 Catalysts 2019, 9, 238 4 of 10 9 1.0 Catalysts 2019, 9, 238 3 of 10 9 8 0.8 (Figures 3 and 4; Supplementary Material Figures S15–17),1.0 along with a considerable amount of (Figures 3 and 4; Supplementary Material Figures S15–17),0.6 along with a considerable amount of 100 Catalysts 2019, 9, 238 carbazole. 7 3 of 10 0.8 carbazole. 8 0.4 0.6 90 6 Amount(µmol) 0.2 100 7 9 0.4 80 9 1.0 0.0 1.0 C3 C4 C5 C6 C7 C8 C9 C10

90 5 0.8 Amount(µmol) 0.2 Alkane metathasis products 6 8 0.8 70 8 0.6 80 0.6 0.0 4 7 C3 C4 C5 C6 C7 C860 C9 C10 5 7 0.4 0.4 Alkane metathasis products

70 Amount(µmol) 0.2

6 Amount(µmol) 3 6 0.2 50 Amount (µmol) 4 0.0 60 0.0 C3 C4 C5 C6 C7 C8 C9 C10 5 AlkaneC3 C4 metathasis C5 C6 C7 C8products C9 C10 40 2 5 Alkane metathasis products Conversion (%) 50 3 4 Amount (µmol) 4 30 1 40 3 2 Amount (µmol) 3 20 Amount (µmol) Conversion (%) 0 30 2 2 10

1 cC2 cC3 cC4 cC5 cC7 cC8 cC9

20 1 cC10 cC11 cC12 cC13 1 0 0 0 20406080100120 10 0 Carbazole 0 Time (h) cC2 cC3 cC4 cC5 cC7 cC8 cC9 cC2 cC3 cC4 cC5 cC7 cC8 cC9 cC10 cC11 cC12 cC13 cC2 cC3 cC4 cC5 cC7 cC8 cC9 0 cC10 cC11 cC12 cC13 cC10 cC11 cC12 cC13 0 20406080100120Figure 3. Product distribution: Functionalized alkane metathesis products ( ), alkane metathesis Carbazole Carbazole Timeproducts (h) ( ), and carbazole ( )Carbazole after 30 days of reaction.Figure 2. Metathesis of 1-Alkyl-2,5-Dimethyl-1H-pyrrole, conversion versus time plot. ( ) Reaction Figure 3. Product distribution: Functionalized alkane metathesis products ( ), alkane metathesis Figure 3. Product distribution: Functionalized alkane at room me metathesis temperaturetathesis products (RT); ( ),), reaction alkane( metathesisat 150 °C. Figure 3. Productproducts ( distribution: ), and carbazole Functionalized( ) after 30 days of reaction.alkane metathesis products ( ), alkane metathesis Figure 2. Metathesis of 1-Alkyl-2,5-Dimethyl-1H-pyrrole, conversionproductsp ( versus), and and carbazoletime carbazole plot ( ( )) after.Reactionafter ( ) 30 30 days days of of reaction. reaction. at room temperature (RT); ( ) reaction at 150products °C. rodu ( ct ), and carbazole ( ) after 30 days of reaction.The product was analyzed by gas chromatography (GC), gas chromatography coupled with 9 s ( , mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy, confirming the 9 The product was analyzed by gas chromatography (GC), gas chromatography8 9 coupled withformation of expected product 1,4-bis-(2,5-Dimethyl-1H-pyrrole-1yl)but-2-ene, with 85% conversion 8 mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy,7 8 confirming theand a turnover number (TON) of 850 (Figure 2) [20–22]. These results clearly indicated that our 9 7 7 formation of expected product 1,4-bis-(2,5-Dimethyl-1H-pyrrole-1yl)but-2-ene, with6 85% conversioncatalyst was capable of carrying out the olefin metathesis reaction for this particular substrate, 6 and a turnover number (TON) of 850 (Figure 2) [20–22]. These results clearly8 indicated6 that ourwhereas in the case of 1-Propyl-2,5-Dimethyl-1H-pyrrole 2 or 1-Hexyl-2,5-Dimethyl-1H-pyrrole 3, no 5 5 catalyst was capable of carrying out the olefin metathesis reaction for this 7particular5 substrate,metathesis was observed. The limiting step in the latter case was the alkyl chain C-H activation (as 4 4 whereas in the case of 1-Propyl-2,5-Dimethyl-1H-pyrrole 2 or 1-Hexyl-2,5-Dimethyl-1H-pyrrole4 3, noan entry into the alkane metathesis productive cycle). During the catalytic reaction, we understood 6 3 metathesis was observed. The limiting step in the latter case was the alkyl chain 3C-H (µmol) Amount 3 activation (asthat isomerization of the substrates occurs because of walking of α-methyl groups on the ring [23]. Amount (µmol) Amount Amount (µmol) Amount 5 2 an entry into the alkane metathesis productive cycle). During the catalytic reaction,2 2 we understoodTo avoid that, we thought to synthesize 9-Hexyl-9H-carbazole (a rigid molecule) to carry out the 1 that isomerization of the substrates occurs because of walking of α-methyl groups4 on1 the ring [23].metathesis reaction. 9-Hexyl-9H-carbazole was obtained by the reaction of carbazole and hexyl 1 0 To avoid that, we thought to synthesize 9-Hexyl-9H-carbazole (a rigid molecule) to0 carry out thebromide in the presence of KOH, by following a literature procedure (Scheme 2) [24]. 3 cC2 cC3 cC4 cC5 cC7 cC8 cC9

Amount (µmol) Amount 0 cC10 cC11 cC12 cC13 metathesis reaction. 9-Hexyl-9H-carbazole was obtained by the reaction of carbazole cC2 andcC3 hexylcC4 cC5 cC7 cC8 cC9 cC10 cC11 cC12 cC13

cC2 cC3 cC4 cC5 cC7 cC8 cC9 Hexyl Bromide bromide in the presence of KOH, by following a literature procedure (Scheme 2)2 [24]. cC10 cC11 cC12 cC13 KOH Figure 4. Product distribution: 1 Functionalized alkane metathes metathesisis products over time ( )) 5 days; ( DMF )) Hexyl Bromide Figure 4. Product distribution: Functionalized alkane metathesis products over time ( ) 5 days; ( ) RT, 9h KOH 10 days; ( )) 30 30 30 days. days. N N Figure 4. Product distribution:0 Functionalized alkane metathesis products overH time ( ) 5 days; ( ) DMF 1 2 cC2 cC3 cC4 cC5 cC7 cC8 cC9

RT, 9h10 days;The ( formation) 30 days. of the dimer [1,10-di(9H-carbazole-9-yl-)decane]cC10 cC11 wascC12 understandablecC13 as it is the 3 N The formationN of the dimer [1,10-di(9H-carbazole-9-yl-)decane] was understandable5 as it 6 H 4 isself-metathesis the self-metathesis1 2 product product of the 9-(hex-5en-1-yl)-9 of the 9-(hex-5en-1-yl)-9HH carbazole carbazole (Supplementary (Supplementary Material Figures Material S15 is the self-metathesis product of the 9-(hex-5en-1-yl)-9H carbazole (Supplementary Material 5 Figuresand S16). S15 Initially, and3 16). 9-(hex-5en-1-yl)-9 Initially, 9-(hex-5en-1-yl)-9HH carbazole (dehydrogenation carbazole (dehydrogenation product of 9-Hexyl-9 productH-carbazole) of 9- 6 5 TheFigures formation S156 and4 of 16). the Initially, dimer 9-(hex-5en-1-yl)-9H[1,10-di(9H-carbazo carbazolele-9-yl-)decane] (dehydrogenation was understandableproduct of 9- as it FigureHexyl-9H-carbazole)was 4. Product formed by distribution: the reaction was of formedFunctionalized [(≡Si-O-)W(CH by the reaction3 alkane)5] 1 and metathesof 9-Hexyl-9 [(≡Si-O-)W(CHHis-carbazole products3)5] (Figures1 over and time9-Hexyl-9H- S13 and( ) S14). 5 days; ( ) is the self-metathesisHexyl-9H-carbazole)5 product was formed of the by 9-(hex-5 the reactionen-1-yl)-9H of [(≡Si-O-)W(CH carbazoleScheme3)5] (Supplementary1 and2. Synthesis 9-Hexyl-9H- of 9-Hexyl-9H-carbazole Material 6. carbazoleOther N-Alkyl (Figures carbazoles6 S13 and and alkanes14). Other were N formed-Alkyl duecarbazoles to chain and walking alkanes (our activewere catalystformed containsdue to Figures10 days;carbazole S15( ) and30 days.(Figures 16). Initially, S13 and 9-(hex-5en-1-yl)14). Other N-Alkyl-9H carbazoles carbazole and alkanes(dehydrogenation were formed due product to of 9- Scheme 2. Synthesis of 9-Hexyl-9H-carbazolechainW-H) followedwalking by(our 6. cross active metathesis catalyst with contains linear olefins,W-H)In a typicalfollowed and, atreaction, the by end, cross 9-Hexyl-9H-carbazole reduction metathesis of newly with formed 6linear and [( ≡Si-O-)W(CH3)5] 1, in 50:1 molar ratio, based Hexyl-9H-carbazole)olefins,olefins toand, new at alkanes. the was end, Lookingformed reduction at by the of productthenewly reaction formed distribution, olefinsof [( we≡ Si-O-)W(CHto observed new alkanes. that,3 along) 5Looking] 1 withand atall 9-Hexyl-9H- the the The formationolefins, and, of at thethe end,dimer reduction [1,10-di(9H-carbazo of newlyon loadingformed ofolefinsle-9-yl-)decane] W, were to mixed.new alkanes. The mixturewas Looking understandable was sealedat the in an ampoule as it tube under high vacuum and In a typical reaction, 9-Hexyl-9H-carbazolecarbazole 6 andproductmetathesis [(≡ Si-O-)W(CH(Figures distribution, products S133)5] 1, ofand in thewe50:1 14). functionalized observedmolar Other ratio, that, basedN alkanes,-Alkyl thealon reactiong a carbazoleswith considerable continued all the amountandatmetathesis 150 alkanes °C. of TheN -alkaneproducts first were sample metathesis formedof wasthe quenched due to with dichloromethane and injected on loading of W, were mixed. The mixtureis the waschain self-metathesis sealed walkingfunctionalizedproducts in an ampoule and (our carbazole alkanes, product activetube under were acatalyst considerable of high formed. the vacuum contains9-(hex-5 In amountN -alkaneandin GCW-H)en-1-yl)-9H of metathesis afterN-alkane followedone day products,metathesis carbazoleof reaction.by the cross products concentration To (Supplementary metathesisour and surprise carbazole of the, neitherwith C6 linearanyMaterial cons iderable amount of product nor the reaction continued at 150 °C. The first sample waswere(hexane) quenched formed. was with higher, In dichloromethane N-alkane as compared metathesis and to its injected lower products,decomposition and higher the concentration homologues. of the starting Theseof materialthe products C6 (hexane) (9-Hexyl could -9H-carbazole) onlywas were observed. We continued the Figuresolefins, S15were and, and formed. at 16). the Initially, Inend, N-alkane reduction 9-(hex-5en-1-yl) metathesis of newly products, formed-9H the carbazole concentration olefins to (dehydrogenation newof the alkanes. C6 (hexane) Looking was product at the of 9- in GC after one day of reaction. To our surprise, neitherhigher,form ifany the as cons catalystcomparediderable attacks to amount its the lower position of productand 1 ofhigher the norreaction 9-Hexyl-9 homologues. forH-carbazole another These four (Scheme products days.2 andAfter could Figure five only5 ),days, forming form the if reaction mixture was taken, quenched with Hexyl-9H-carbazole)producthigher, distribution, as compared was we toformed itsobserved lower byand that,thehigher reaction alon homologues.g with of [(Theseall≡Si-O-)W(CH the products metathesis could3)5 ]only 1products and form if9-Hexyl-9H- of the decomposition of the starting material (9-Hexyl-9H-carbazole)the W-Ccatalyst bond were attacks followed observed. the by position reduction We continued 1 ofof the the the N-Cdichloromethane, 9-Hexyl-9H-carbazole bond to generate filtered, carbazole (Scheme and analyzed and the2 and W-Alkyl by FigureGC. We chain 5), could observe a range of alkylated carbazoles, carbazolefunctionalized the(Figures catalyst alkanes, S13attacks and athe considerable 14). position Other 1 of amountN the-Alkyl 9-Hexyl-9H-carbazole of carbazoles N-alkane metathesis and (Scheme alkanes products2 and were Figure and formed 5), carbazole due to reaction for another four days. After five days, theforming(Figure reaction5). the mixture Furthermore, W-C bondwas taken,followed the W-Alkyl quenched by reduction chain with underwentstarting of the from N-C an cC 2αbond to-H cC abstraction 10to, with generate a conversion and carbazoleβ-H of elimination, starting and the material of 2.5% and the formation of carbazole dichloromethane, filtered, and analyzedchain by wereGC. walking We formed. W-Alkylgeneratingcould observe(our chainIn W-carbene Nactive a (Figure -alkanerange and ofcatalyst 5). alkylated olefin. metathesisFurthermor Additionally, containscarbazoles,e, products,theitself W-Alkyl W-carbene W-H) (Figures thechain followed and 3 concentrationand olefinunderwent 4). underwentWhile by an crosscarrying α -Hof an abstraction olefinthemetathesis out C metathesisthe6 reaction(hexane) and with with was 1linear, we thought the reaction would go starting from cC2 to cC10, with a conversionolefins, ofhigher, starting and,βreaction, materialas-H atcomparedelimination, the generatingof 2.5% end, and togenerating a reduction the rangeits formation lower of N -alkaneW-carbene and ofof carbazole productsnewlyhigher smoother,and (Choformed 3olefin.–Cmologues.10 as), aftertheAdditionally, olefins lone reduction Thesepair wasto of products W-carbenenew thedelocalized newly-formed alkanes. couldinand the olefinscarbazoleolefin Lookingonly form conjugated at if the system and there was no labile itself (Figures 3 and 4). While carrying out the reactionunderwent(Figure with5). 1 The, wean various thoughtolefin metathesisN the-Alkyl reaction carbazoles reaction, would were gogroupgenerating formed on the by a activationring.range To of our N of-alkane positionsurprise products, 6 we (Scheme only (C 2obtained)3 of–C the10), 5.0% conversion, even after 30 days. While the catalystunderwent attacks an olefin the metathesisposition 1reaction, of the generating 9-Hexyl-9H-carbazole a range of N-alkane (Scheme products 2 (Cand3–C 10Figure), 5), smoother, as the lone pair was delocalizedproduct in the carbazole distribution,after reductionconjugated ofsystemwe the newly-formedobserved and there was that,no olefins labile analyzingalon (Figureg the5).with Thereaction variousall mixture,the N -Alkylmetathesis we observed carbazoles linearproducts were alkanes (alkaneof the metathesis products), N-Alkyl formingafter the reduction W-C bond of the followed newly-formed by reduction olefins (Figure of the 5). N-CThe various bond toN-Alkyl generate carbazoles carbazole were and the group on the ring. To our surprise, wefunctionalized only obtainedformed 5.0% alkanes, byconver activationsion, a considerableeven of position after 30 days.6 (Scheme amount Whilecarbazoles 2) of of the N alkyl-alkaneand thechain dimer metathesis of the of 9-Hexyl-9H-carbazole.9-Hexyl-9H-carbazole products and(functionalized carbazole alkane metathesis products) analyzing the reaction mixture, we observedW-Alkyl linear alkanes chain (alkane (Figure metathesis 5). Furthermor products), Ne,-Alkyl the W-Alkyl chain underwent an α-H abstraction and were formed. In N-alkane metathesis products, the concentration of the C6 (hexane) was carbazoles and the dimer of 9-Hexyl-9H-carbazoleβ-H elimination,(functionalized generating alkane metathesis W-carbene products) and olefin. Additionally, W-carbene and olefin higher, as compared to its lower and higher homologues. These products could only form if underwent an olefin metathesis reaction, generating a range of N-alkane products (C3–C10), the aftercatalyst reduction attacks of thethe newly-formedposition 1 of olefins the 9-Hexyl-9H-carbazole (Figure 5). The various (SchemeN-Alkyl carbazoles 2 and Figure were 5), formingformed the by W-C activation bond followedof position by 6 (Schemereduction 2) of thethe alkyl N-C chainbond ofto the generate 9-Hexyl-9H-carbazole. carbazole and the W-Alkyl chain (Figure 5). Furthermore, the W-Alkyl chain underwent an α-H abstraction and β-H elimination, generating W-carbene and olefin. Additionally, W-carbene and olefin underwent an olefin metathesis reaction, generating a range of N-alkane products (C3–C10), after reduction of the newly-formed olefins (Figure 5). The various N-Alkyl carbazoles were formed by activation of position 6 (Scheme 2) of the alkyl chain of the 9-Hexyl-9H-carbazole.

Catalysts 2019, 9, 238 5 of 10 Catalysts 2019, 9, 238 5 of 10 alkylEven chainthough of thewe 9-Hexyl-9metathesizedH-carbazole. a functionalized Even though alkane, we metathesizedwe could only a ac functionalizedhieve 5.0% conversion alkane, we couldwith a only TON achieve of 2. We 5.0% believe conversion the low with conversion a TON of 2was. We due believe to the the poisoning low conversion of the catalyst was due by to the poisoningformation ofofthe carbazole catalyst (Figure by the formation 5) during of the carbazole reaction (Figure (since5 )the during N-H the of carbazole reaction (since was the no N-Hlonger of carbazoleprotected, was it could no longer attack protected, the catalyst it could and attack deactivate the catalyst it for andfurther deactivate reaction). it for further reaction).

Figure 5. Proposed mechanism for the functionalized alkane metathesis reaction. Figure 5. Proposed mechanism for the functionalized alkane metathesis reaction.

3. Conclusions. Conclusions For thethe first first time, time, we we carried carried out aout functionalized a functiona alkanelized alkane metathesis metathesis reaction usingreaction silica-supported using silica- 3 5 catalystsupported [(≡ catalystSi-O-)W(CH [(≡Si-O-)W(CH3)5] 1, with a) conversion] 1, with a ofconversion 5.0%; N-alkane of 5.0%; metathesis N-alkane was metathesis also observed was also due toobserved the reaction due course.to the Toreaction avoid catalystcourse. decomposition,To avoid catalyst we chosedecomposition, 9-Hexyl-9-H we-carbazole, chose 9-Hexyl-9-H- whereby the lonecarbazole, pair was whereby delocalized the lone in pair the conjugatedwas delocalized system. in the Our conjugated study shows system. that Our the catalyststudy shows decomposes that the becausecatalyst ofdecomposes the reaction because of the N-Hof the of reaction the carbazole of the withN-H theof the catalyst. carbazole Currently, with the we catalyst. are focusing Currently, on the developmentwe are focusing of aon robust the development catalyst for the of functionalized a robust catalyst alkane for metathesisthe functionalized reaction. alkane metathesis reaction. 4. Materials and Methods 4. Materials and Methods 4.1. General Experimental Procedures 4.1. GeneralAll experiments Experimental were Procedures carried out by using standard Schlenk and glove box techniques under an inertAll nitrogenexperiments atmosphere. were carried The out syntheses by using and standa the treatmentsrd Schlenk and of the glove surface box speciestechniques were under carried an − outinert using nitrogen high atmosphere. vacuum lines The (<10 syntheses5 mbar) and and the glove-box treatments techniques. of the surface Pentane species was were distilled carried from out ausing Na/K high alloy vacuum under lines N2 and(<10− dichloromethane5 mbar) and glove-box from techniques. CaH2. Both Pentane solvents was were distilled degassed from through a Na/K freeze-pump-thawalloy under N2 and dichloromethane cycles. SiO2-700 fromwas CaH prepared2. Both from solvents Aerosil were silica degassed from through Degussa freeze-pump- (Frankfurt, 2 ◦ Germany)thaw cycles. (specific SiO2-700 areawas prepared of 200 m from/g), whichAerosil were silicapartly from Degussa dehydroxylated (Frankfurt, at 700Germany)C under (specific high −5 2 vacuumarea of 200 (<10 m2/g),mbar) which for were 24 h partly to give dehydroxylated a white solid, having at 700 °C a specific under high surface vacuum area of (<10 190−5 mmbar)/g and for 2 containing24 hours to aroundgive a white 0.5–0.7 solid, OH/nm having. a W(CHspecific3) 6surface(Figures area S1–S3) of 190 andm2/g supported and containing pre-catalyst around 10.5–0.7were preparedOH/nm2. W(CH according3)6 (Figures to literature S1–3) and procedures supported (Figure pre-catalyst S4) [25 1– 27were]. 2,5-hexanedione, prepared according hexylbromide, to literature hexylamine,procedures propylamine,(Figure S4) allylamine,[25–27]. 2,5-hexanedione, carbazole, C2-C13 -alkylbromides,hexylbromide, andhexylamine, 1,10-dibromodecane propylamine, were purchasedallylamine, from carbazole, Aldrich. C2-C13-alkylbromides, and 1,10-dibromodecane were purchased from Aldrich. NMR spectra were recorded on Bruker Avance IIIIII 500 MHz NMR spectrometer (Bruker Biospin AG, Fallanden,Fallanden, Switzerland) equipped with a BBFO CryoProbe (Bruker). IR spectra were recorded on a Nicolet 6700 FT-IR spectrometerspectrometer (Thermo FisherFisher Scientific,Scientific, Waltham, MA, USA) by using a DRIFT cell equipped with CaF2 windows (Figure S4). The IR samples were prepared under argon within a glove box. Typically, 64 scans were accumulated for each spectrum (resolution 4 cm−1). GC

Catalysts 2019, 9, 238 6 of 10

DRIFT cell equipped with CaF2 windows (Figure S4). The IR samples were prepared under argon Catalysts 2019, 9, 238 6 of 10 within a glove box. Typically, 64 scans were accumulated for each spectrum (resolution 4 cm−1). GC measurements were performed with an Agilent 7890A Series (FID detection; Santa Clara, CA, USA). measurements were performed with an Agilent 7890A Series (FID detection; Santa Clara, CA, USA). Method for GC analyses: Column HP-5; 30 m length × 0.32 mm ID × 0.25 µm film thickness; flow rate, Method for GC analyses: Column HP-5; 30 m length × 0.32◦ mm ID × 0.25 μm film thickness;◦ flow rate, 1 mL/min (N2); split ratio, 50/1; inlet temperature, 250 C, detector temperature, 250 C; temperature 1 mL/min (N2); split ratio, 50/1; inlet temperature, 250 °C, detector temperature, 250 °C; temperature program, 40 ◦C (3 min), 40–250 ◦C (12 ◦C/min), 250 ◦C (3 min), 250–300 ◦C (10 ◦C/min), 300 ◦C program, 40 °C (3 minutes), 40–250 °C (12 °C/min), 250 °C (3 minutes), 250–300 °C (10 °C/min), 300 °C (3 (3 min); 9-hexyl-9H-carbazole retention time, tR = 21.67 min. GC-MS measurements were performed minutes); 9-hexyl-9H-carbazole retention time, tR = 21.67 minutes. GC-MS measurements were with an Agilent 7890A Series coupled with an Agilent 5975C Series. A GC-MS, equipped with a performed with an Agilent 7890A Series coupled with an Agilent 5975C Series. A GC-MS, equipped capillary column coated with none polar stationary phase HP-5MS, was used for molecular weight with a capillary column coated with none polar stationary phase HP-5MS, was used for molecular determination and identification, which allowed the separation of chemical compounds according to weight determination and identification, which allowed the separation of chemical compounds their boiling point differences. Method for GC-MS analyses: Column HP-5MS; 30 m length × 0.25 mm according to their boiling point differences. Method for GC-MS analyses: Column HP-5MS; 30 m length◦ ID × 0.25 µm film thickness; flow rate, 1 mL/min (N2); split ratio, 100/1; inlet temperature, 220 C, × 0.25 mm ID × 0.25 μm film thickness; flow rate, 1 mL/min (N2); split ratio, 100/1; inlet temperature, detector temperature, 300 ◦C; temperature program, 150 ◦C (0 min), 150–300 ◦C (20 ◦C/min), 300 ◦C 220 °C, detector temperature, 300 °C; temperature program, 150 °C (0 minutes), 150–300 °C (20 (30 min). °C/min), 300 °C (30 minutes). HPLC-MS analysis was performed at Core Lab ACL KAUST. The separation of the HPLC-MS analysis was performed at Core Lab ACL KAUST. The separation of the 1,10-di(9H- 1,10-di(9H-carbazole-9yl-)decane from the metathesis reaction mixture was performed using an Accela carbazole-9yl-)decane from the metathesis reaction mixture was performed using an Accela HPLC HPLC System and a hypersil gold 2.1 × 50 mm (Thermo Fisher Scientific, Waltham, MA, USA). 1 mg System and a hypersil gold 2.1 × 50 mm (Thermo Fisher Scientific, Waltham, MA, USA). 1 mg of the of the sample was dissolved in 1 mL (methanol:chloroform), the liquid compound was then diluted sample was dissolved in 1 mL (methanol:chloroform), the liquid compound was then diluted ×1000 ×1000 in 1 mL of methanol. The separation was achieved using a gradient composed of water and in 1 mL of methanol. The separation was achieved using a gradient composed of water and methanol. methanol. The mobile phase solvents were composed of (a) 100% water plus 0.1% formic acid, and The mobile phase solvents were composed of a) 100% water plus 0.1% formic acid, and b) 100% (b) 100% methanol plus 0.1% formic acid. The gradient elution program is summarized in Table S1. methanol plus 0.1% formic acid. The gradient elution program is summarized in Table S1. The injection The injection volume was 10 µL. The flow rate was 400 µL/min. The data processing was performed volume was 10 μL. The flow rate was 400 μL/min. The data processing was performed using Xclaibur using Xclaibur Software (Thermo Fisher Scientific). The mass analysis was performed using a Thermo Software (Thermo Fisher Scientific). The mass analysis was performed using a Thermo LTQ Velos LTQ Velos Orbitrap mass spectrometer (Thermo Scientific, Pittsburgh, PA, USA) equipped with a Orbitrap mass spectrometer (Thermo Scientific, Pittsburgh, PA, USA) equipped with a heated heated electron spray ionization (ESI) ion source. The mass scan range was set to 100–1000 m/z, with electron spray ionization (ESI) ion source. The mass scan range was set to 100–1000 m/z, with a a resolving power of 100,000. The m/z calibration of the LTQ-Orbitrap analyzer was performed in resolving power of 100,000. The m/z calibration of the LTQ-Orbitrap analyzer was performed in the the positive ESI mode, using a solution containing caffeine, MRFA (met-arg-phe-ala) peptide, and positive ESI mode, using a solution containing caffeine, MRFA (met-arg-phe-ala) peptide, and Ultramark 1621 according to the manufacturer’s guidelines. The ESI was performed with a heated Ultramark 1621 according to the manufacturer’s guidelines. The ESI was performed with a heated ion source equipped with a metal needle and operated at 4 kV. The source vaporizer temperature was ion source equipped with a metal needle and operated at 4 kV. The source vaporizer temperature adjusted to 350 ◦C, the capillary temperature was set at 250 ◦C, and the sheath and auxiliary gases was adjusted to 350 °C, the capillary temperature was set at 250 °C, and the sheath and auxiliary were optimized and set to 40 and 20 arbitrary units. gases were optimized and set to 40 and 20 arbitrary units. 4.2. Synthesis of N-Hexyl-Pyrrole 4.2. Synthesis of N-Hexyl-Pyrrole N-Hexyl-pyrrole was synthesized according to literature procedure [17,18]. N-Hexyl-pyrrole was synthesized according to literature procedure [17,18]. 4.3. Synthesis of N-Hexyl-2,5-Dimethyl-Pyrrole 2, N-Propyl-2,5-Dimethyl-Pyrrole 3 and 4.3.N-Allyl-2,5-Dimethyl-Pyrrole Synthesis of N-Hexyl-2,5-Dimethyl-Pyrrole 4 2, N-Propyl-2,5-Dimethyl-Pyrrole 3 and N-Allyl-2,5- Dimethyl-Pyrrole 4 Compounds 2, 3, 4 were synthesized according to the Paal-Knorr method of pyrrole synthesis (SchemeCompounds3). 2, 3, 4 were synthesized according to the Paal-Knorr method of pyrrole synthesis (Scheme 3).

Scheme 3. Synthesis of N-alkyl-alkyl pyrroles. pyrroles.

• General• General Procedure Procedure for 2, 3 ,for4 (Figures 2, 3, 4 (Figures S5–S10): S5–10): 2,5-hexanedione (10 mmol) was dissolved in MeOH (50 mL) and the respective primary amine (10 mmol) was added at room temperature (RT). The reaction was slightly exothermic and the cooling by ice bath was recommended when higher quantities were used for reaction. Reaction mixture (RM) was stirred for 10 minutes at RT and evaporated in vacuum. Hexane was added to the RM and the water phase separated from the organic phase. The organic phase was dried over MgSO4, filtered, and evaporated to dryness. The product was purified by flash-column chromatography

Catalysts 2019, 9, 238 7 of 10

2,5-hexanedione (10 mmol) was dissolved in MeOH (50 mL) and the respective primary amine (10 mmol) was added at room temperature (RT). The reaction was slightly exothermic and the cooling by ice bath was recommended when higher quantities were used for reaction. Reaction mixture (RM) was stirred for 10 min at RT and evaporated in vacuum. Hexane was added to the RM and the water phase separated from the organic phase. The organic phase was dried over MgSO4, filtered, and evaporated to dryness. The product was purified by flash-column chromatography (Hexane:EtOAc = 4:1), distilled over sodium in vacuum, and degassed prior to use. The reference N-Alkyl-2,5-Dimethyl-pyrroles (C2–C9) were synthesized with the same procedure and used as standards in GC-MS analysis. Yields were in range 60–70%.

1 N-Hexyl-2,5-Dimethyl-pyrrole 2. H NMR (C6D6), δ, ppm (J, Hz): 6.04 (2H, s, CH Ar), 3.35–3.32 (2H, t, J = 7.2, N-CH2), 2.09 (6H, s, 2 × Ar CH3), 1.36–1.30 (2H, m, CH2), 1.18–1.14 (2H, m, CH2), 1.07–1.04 13 (4H, m, 2 × CH2), 0.85–0.82 (3H, t, J = 7.2, CH3). C NMR (C6D6): 126.7, 106.2, 43.5, 31.8, 31.4, 26.8, 22.9, 14.2, 12.7.

1 N-Propyl-2,5-Dimethyl-pyrrole 3. H NMR (C6D6), δ, ppm (J, Hz): 6.02 (2H, s, CH Ar), 3.27–3.24 (2H, t, J = 7.5, N-CH2), 2.05 (6H, s, 2 × Ar CH3), 1.34–1.27 (2H, m, J = 7.4, CH2), 0.63–0.60 (3H, t, J = 7.3, CH3). 13 C NMR (C6D6): 126.8, 106.1, 44.9, 24.5, 12.7, 11.2. 1 N-Allyl-2,5-Dimethyl-pyrrole 4. H NMR (C6D6), δ, ppm (J, Hz): 6.03 (2H, s, CH Ar), 5.50–5.43 (1H, m, CH Allyl), 4.85–4.82 (1H, dd, 1J = 10.3, 2J = 1.8 Hz), 4.57–4.53 (1H, dd, 1J = 10.3, 2J = 1.8 Hz), 3.82–3.80 13 (2H, m, CH2), 2.01 (6H, s, 2 × CH3). C NMR (C6D6): 134.8, 127.1, 114.9, 106.1, 45.2, 12.3.

4.4. 1,4-Bis(2,5-Dimethyl-1-H-Pyrrole-1yl)But-2-Ene 1,4-bis(2,5-dimethyl-1-H-pyrrole-1yl)but-2-ene was separated from N-Allyl-2,5-Dimethyl-pyrrole metathesis reaction mixture as a white solid and characterized by NMR (Figures S11 and S12). 1 H NMR (C6D6), δ, ppm (J, Hz): 6.04 (4H, s, CH Ar), 4.70–4.69 (2H, t, J = 1.2 Hz, 2 × CH), 3.59 13 (4H, d, J = 1 Hz, 2 × CH2), 1.95 (12H, s, CH3). C NMR (C6D6): 127.0, 126.9, 106.1, 43.8, 12.3.

4.5. Synthesis of 9-Hexyl-9H-Carbazole 6 9-Hexyl-9H-carbazole 6 was synthesized according to the literature method with a modification [24]. Procedure: carbazole (37 mmol) was dissolved in DMF (85 mL) under argon, potassium hydroxide (232 mmol) was added to a solution, and the mixture was stirred for 40 min at RT. Hexylbromide (37 mmol) was added dropwise and the RM was stirred for an additional 9 h at RT. After that, RM was poured into water (100 mL). In order to extract the product from the DMF/water mixture, 100 mL of n-hexane and 100 mL of EtOAc were added. The resulting four-component (DMF/water/hexane/EtOAc) mixture was intensively shacked in the separation funnel. The upper organic phase was separated and washed with water (2 × 50 mL). The lower DMF/water phase was additionally extracted by a mixture of hexane (100 mL) and EtOAc (100 mL), and the organic phase was washed with water (2 × 50 mL). The combined organic phase (pure from DMF) was dried over Na2SO4 and evaporated in vacuum. The product was puriﬁed by column chromatography (petroleum ether:DCM = 3:1), recrystallized from hexane (−30 ◦C) and dried on high-vacuum line HVL. Yield: 86%, white needle-like crystals. NMR spectra were in accordance with the literature data (Figures S13 and S14). 1 H NMR (C6D6), δ, ppm (J, Hz): 8.08 (2H, d, J = 7.8 Hz, H Ar), 7.44–7.40 (2H, m, H Ar), 7.25–7.22 (2H, m, H Ar), 7.20–7.18 (2H, m, H Ar), 3.79 (2H, t, J = 7.2 Hz, CH2), 1.51–1.48 (2H, m, CH2), 1.08–1.02 13 (6H, m, 3 × CH2), 0.79–0.76 (3H, t, J = 7 Hz, CH3). C NMR (C6D6): 140.9, 125.9, 123.5, 120.8, 119.2, 109.0, 42.9, 31.8, 29.0, 27.1, 22.8, 14.2. Catalysts 2019, 9, 238 8 of 10

4.6. Synthesis of 9-Hexyl-9H-Carbazole Metathesis Products

The metathesis products (N-Alkyl-carbazoles, C2–C13) were additionally prepared as reference compounds, according to the procedure from Section 4.5. and used for GC-MS analysis without further puriﬁcation. The retention time and fragmentation of the reference compounds exactly matched the products from the 9-Hexyl-9H-carbazole metathesis reaction, proving their linear structure. Retention times for N-alkylated carbazoles: C2 4.73 min, C3 5.11 min, C4 5.55 min, C5 5.98 min, C6 (starting material) 6.51 min, C7 6.87 min, C8 7.27 min, C9 7.67 min, C10 8.13 min, C11 8.63 min, C12 9.20 min, and C13 9.86 min.

4.7. 1,10-Di-(9H-Carbazole-9yl-)-Decane (C34H37N2) 1,10-di-(9H-carbazole-9yl-)-decane was synthesized as a reference compound, according to the procedure from Section 4.5., with 1,10-dibromodecane as an alkylation agent, and used for HPLC-MS analysis of the reaction mixture (Figures S15–S17). 1 H NMR (C6D6), δ, ppm (J, Hz): 8.07 (4H, d, J = 7.7, H Ar), 7.43–7.40 (4H, m, H Ar), 7.24–7.19 (8H, 13 m, H Ar), 3.81 (4H, t, J = 7, 2 × N-CH2), 1.54–1.48 (4H, m, 2 × CH2), 1.05–0.95 (12H, m, 6 × CH2). C NMR (C6D6): 140.9, 125.9, 123.5, 120.9, 119.3, 109.0, 42.9, 29.6, 29.1, 27.4. Theoretically predicted isotopic distribution of C34H37N2: 473.29513, 474.29848, 475.30184 (δ = 0 ppm). Experimentally found isotopic distribution of the reference compound: 473.29497, 474.29824, 475.30157 (δ = −0.335 ppm). Experimentally-found isotopic distribution of the dimer found in the reaction mixture: 473.29506, 474.29837, 475.30188 (δ = −0.147 ppm).

4.8. Catalytic Reactions

9-Hexyl-9H-carbazole 6 (200 mg, 0.8 mmol) and [(≡Si-O-)W(CH3)5] 1 (100 mg, 0.016 mmol W) were mixed in the ampule tube in the glove box; the ampule tube was connected to a high-vacuum line and sealed in a vacuum. The ampule was then heated at 150 ◦C with stirring (50 rpm). Quenching: the ampule was cooled down in liquid nitrogen, opened, 1 mL of DCM was added, the mixture was ﬁltered through a syringe ﬁlter (1 µm), and the sample was analyzed by GC. 1-Hexyl-2,5-Dimethyl-1H-pyrrole 2, 1-Propyl-2,5-Dimethyl-1H-pyrrole 3, and 1-Allyl-2,5- Dimethyl-1H-pyrrole 4 were analyzed with the same procedure.

Supplementary Materials: The following are available online at http://www.mdpi.com/2073-4344/9/3/238/s1, 1 13 Table S1: Gradient elution program, Figure S1: H NMR spectrum of WMe6 in CD2Cl2 at 203 K, Figure S2: C 2 1 13 NMR spectrum of WMe6 in CD2Cl2 at 203 K, Figure S3: D solution H- C Heteronuclear Single Quantum Correlation (HSQC) NMR spectrum of WMe6 in CD2Cl2 at 203 K, Figure S4: FT-IR spectroscopy of silica o partially dehydroxylated at 700 C (SiO2–700) (blue curve) and W(CH3)6 grafted on SiO2–700 (1) (orange curve), 1 13 Figure S5: H NMR spectrum of N-Hexyl-2,5-Dimethyl-pyrrole 2 in C6D6, Figure S6: C NMR spectrum 1 of N-Hexyl-2,5-Dimethyl-pyrrole 2 in C6D6, Figure S7: H NMR spectrum of N-Propyl-2,5-Dimethyl-pyrrole 13 3 in C6D6, Figure S8: C NMR spectrum of N-Propyl-2,5-Dimethyl-pyrrole 3 in C6D6, Scheme S1: No functionalized alkane metathesis product was observed using substrate 2 and 3, Figure S9: 1H NMR spectrum 13 of N-Allyl-2,5-Dimethyl-pyrrole 4 in C6D6, Figure S10: C NMR spectrum of N-Allyl-2,5-Dimethyl-pyrrole 1 4 in C6D6, Figure S11: H NMR spectrum of 1,4-bis(2,5-dimethyl 1-H-pyrrole-1yl)but-2-ene in C6D6, Figure 13 1 S12: C NMR spectrum of 1,4-bis(2,5-dimethyl 1-H-pyrrole-1yl)but-2-ene in C6D6, Figure S13: H NMR 13 spectrum of 9-Hexyl-9H-carbazole in C6D6, Figure S14: C NMR spectrum of 9-Hexyl-9H-carbazole 1 13 in C6D6, Figure S15: H NMR spectrum of 1,10-di(9H-carbazole-9yl-)decane in C6D6, Figure S16: C NMR spectrum of 1,10-di(9H-Carbazole-9yl-)decane in C6D6, Figure S17: Comparison of the reference 1,10-di-(9H-carbazole-9yl-)-decane (C34H37N2) with the dimer found in 9-Hexyl-9H-carbazole metathesis reaction mixture. Author Contributions: Conceptualization, M.T., Y.L., M.K.S., M.R. and J.-M.B.; experiments, M.T., Y.L., A.S.; writing M.T., M.K.S., and J.-M.B. Funding: This work was supported by funds from King Abdullah University of Science and Technology (KAUST). Acknowledgments: The authors acknowledge Salim Sioud (KAUST ACL Core Lab), Kristina Smirnova and Miguel Dinis Veloso Guerreiro for technical assistance. Catalysts 2019, 9, 238 9 of 10

Conﬂicts of Interest: The authors declare no competing ﬁnancial interests.

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