inorganics

Article Mechanistic Implications for the Ni(I)-Catalyzed Kumada Cross-

Linda Iffland 1, Anette Petuker 1, Maurice van Gastel 2 and Ulf-Peter Apfel 1,* ID

1 Anorganische Chemie I, Ruhr-Universität Bochum, Universitätsstraße 150, 44801 Bochum, Germany; Linda.Iffl[email protected] (L.I.); [email protected] (A.P.) 2 Max-Planck-Institut für Chemische Energiekonversion, Stiftstraße 34-36, 45470 Mülheim, Germany; [email protected] * Correspondence: [email protected]; Tel.: +49-234-322-4187

Received: 9 October 2017; Accepted: 10 November 2017; Published: 14 November 2017

Abstract: Herein we report on the cross-coupling reaction of with aryl halides using the well-defined tetrahedral Ni(I) complex, [(Triphos)NiICl] (Triphos = 1,1,1- tris(diphenylphosphinomethyl)ethane). In the presence of 0.5 mol % [(Triphos)NiICl], good to excellent yields (75–97%) of the respective coupling products within a reaction time of only 2.5 h 2 II at room temperature were achieved. Likewise, the tripodal Ni(II)complexes [(κ -Triphos)Ni Cl2] 3 II and [(κ -Triphos)Ni Cl](X) (X = ClO4, BF4) were tested as potential pre-catalysts for the Kumada cross-coupling reaction. While the Ni(II) complexes also afford the coupling products in comparable yields, mechanistic investigations by UV/Vis and electron paramagnetic resonance (EPR) spectroscopy indicate a Ni(I) intermediate as the catalytically active species in the Kumada cross-coupling reaction. Based on experimental findings and density functional theory (DFT) calculations, a plausible Ni(I)-catalyzed reaction mechanism for the Kumada cross-coupling reaction is presented.

Keywords: nickel; tripodal ; cross-coupling; EPR; Grignard; DFT

1. Introduction Metal-catalyzed cross-coupling reactions are an essential tool for the formation of carbon–carbon bonds [1]. Coupling reactions of organometallic reagents with organic electrophiles are industrially utilized for the synthesis of pharmaceuticals, agrochemicals and polymers. Although the first cross-coupling reactions of organomagnesium bromides described by Kumada or Corriu utilized nickel catalysts, for example, [Ni(dppe)Cl2] and Ni(acac)2 [2,3], the most efficient and commonly employed catalysts for such C–C coupling reactions nowadays are based on noble metals [4]. In particular, and its complexes are exhaustively reported for C–C bond formation reactions and mechanistic details of Pd-based catalysts are well understood [5]. Due to the high cost and low abundance of noble metals, the development of alternative catalytic systems based on earth-abundant and less expensive metals, such as nickel and iron, recently attracted much interest. Likewise, Ni(0), Ni(I), Ni(II) and Ni(III) complexes have been proposed as potential intermediates for various C–C coupling reactions including Heck, Hiyama, Kumada, Negishi, Suzuki–Miyaura, Sonogashira and Stille coupling techniques [6–8]. Along this line, Ni(I) as well as Ni(III) species were proposed as reactive intermediates in the nickel-catalyzed coupling of aryl halides by trans-ArNiBr(PEt3)2 [9]. Notably, nickel is substantially more nucleophilic as compared to Pd and Pt due to its smaller atomic size. Because of their higher nucleophilicity, nickel catalysts allow reactions under milder conditions and more challenging electrophiles than can be used in palladium . While numerous examples of low-valent nickel(I) complexes were reported, well-defined stable Ni(I) precursors as catalysts in cross-coupling reactions are rare [10]. Such Ni(I) complexes

Inorganics 2017, 5, 78; doi:10.3390/inorganics5040078 www.mdpi.com/journal/inorganics Inorganics 2017, 5, 78 2 of 13

InorganicsWhile2017 numerous, 5, 78 examples of low-valent nickel(I) complexes were reported, well-defined stable2 of 13 Ni(I) precursors as catalysts in cross-coupling reactions are rare [10]. Such Ni(I) complexes are arefrequently frequently used used as aspotent potent pre-catalysts pre-catalysts in inthe the Negishi coupling of of alkyliodides alkyliodides and alkylzincalkylzinc bromides [[11–13],11–13], in the Suzuki–MiyauraSuzuki–Miyaura reaction for the formation of C–C bonds from arylhalides and phenylboronic acid [14–16], [14–16], as well as in Ni(I)-catalyzed Kumada coupling reactions reactions [17,18]. [17,18]. Here, most commonly, commonly, bulky bulky NN-heterocyclic-heterocyclic carbenes carbenes (NHCs) (NHCs) are are utilized utilized as asa a ligand platform platform for forthe stabilization the stabilization of the of monovalent the monovalent nickel nickel centers. centers. Along this Along line, this Whittlesey line, Whittlesey and coworkers and coworkers reported a series of extremely air-sensitive [NiI(PPh3)(NHC)X]I complexes (X = Br, Cl) (Scheme 1) comprising reported a series of extremely air-sensitive [Ni (PPh3)(NHC)X] complexes (X = Br, Cl) (Scheme1) comprisingbulky NHC bulkyligands NHC [17]. ligandsHerein, [the17]. sterically Herein, dema the stericallynding substitution demanding at substitutionthe central heteroaromatic at the central heteroaromaticring is required ring to isstabilize required the to stabilizelow-coordinate the low-coordinate and low-valent and low-valentNi(I)-complex Ni(I)-complex and to avoid and tointermolecular avoid intermolecular reactions. reactions. The Ni(I) Thecomplexes Ni(I) complexes were subsequently were subsequently studied for studied the Kumada for the Kumadacoupling couplingof aryl chlorides, of aryl chlorides, for example, for example, chlorobenzene and 4-chlorotoluene, and 4-chlorotoluene, with phenylmagnesium with phenylmagnesium chloride chlorideleading to leading 1,1’-biphenyl to 1,10-biphenyl or 4-methyl-1,1’-biphenyl. or 4-methyl-1,10-biphenyl.

Scheme 1. Literature-known monovalent nickel catalysts for the Kumada coupling [[10].10].

Notably, an increase in in both both the the carben carbenee ring ring size size and and steric steric demand demand of of the the N-substituentsN-substituents led led to toa decrease a decrease in incatalytic catalytic activity. activity. Likewise, Likewise, bulkier bulkier cross-coupling cross-coupling partners like mesitylmagnesiummesitylmagnesium bromide or more more challenging challenging substrates substrates (e.g., (e.g., aryl aryl fluorides) fluorides) led led to toa decrease a decrease in inthe the yield yield of the of thebi- bi-arylaryl products products to toless less than than 30%. 30%. Among Among all all Ni(I) Ni(I) sp speciesecies used used for for these these C–C C–C bond bond formation formation studies, studies, I [NiI (6-Mes)(PPh )Br] (6-Mes = 1,3-bis(2,4,6-trimethylphenyl)hexahydropyrimidine-2-ylidene) showed [Ni (6-Mes)(PPh33)Br] (6-Mes = 1,3-bis(2,4,6-trimethylphenyl)hexahydropyrimidine-2-ylidene) showed highest activityactivity forfor the the coupling coupling of of chlorobenzene chlorobenzene and and phenylmagnesium phenylmagnesium chloride chloride with with yields yields up to up 83% to 0 of83% 1,1 of-biphenyl 1,1’-biphenyl [5]. The [5]. efficiency The efficiency of the coupling of the coupling reaction couldreaction further could be further increased be whenincreased complexes when I I [Ni (IPr)(PPh )Cl]I and [Ni (IPr) Cl] (IPrI = 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene) were complexes [Ni3 (IPr)(PPh3)Cl] and2 [Ni (IPr)2Cl] (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazolin-2- appliedylidene) withwere catalystapplied loadingswith catalyst of 1 loadings mol %, affordingof 1 mol %, yields affording of up yields to 98% of up for to the 98% desired for the coupling desired I productcoupling withinproduct reaction within reaction times of times 3 and of 3 18 and h [1818 h,19 [18,19].]. In In analogy, analogy, [Ni [Ni(IMes)I(IMes)2X]2X] (IMes (IMes == 1,3- 1,3- bis(2,4,6-trimethylphenyl)imidazole-2-ylidene, X X = = Br, Br, Cl) Cl) acts acts as a potent catalyst for the Kumada 0 II cross-coupling reaction reaction (Scheme (Scheme 1)1 )[[20].20 When]. When compared compared to [Ni to0(IMes) [Ni (IMes)2] and 2[Ni] andII(IMes) [Ni2X(IMes)2], all three2X2], allcomplexes three complexes revealed revealedsimilar similarcatalytic catalytic activity activity for forthe thereaction reaction of ofchlorobenzene chlorobenzene and mesitylmagnesium bromide under the same experimental conditions and afforded 2,4,6-trimethyl- 0 1,1′-biphenyl in in 73–79% 73–79% yield yield when when 3 3mol mol % % catalyst catalyst was was applied. applied. It is Itworth is worth mentioning mentioning that thatbiscarbene biscarbene Ni(I) Ni(I)complexes complexes were shown were shown to dimerize to dimerize under the under applied the appliedreaction reactionconditions, conditions, forming µ formingdinuclear dinuclear Ni(I)(µ-Cl) Ni(I)(2Ni(I)-Cl) intermediates2Ni(I) intermediates that were that weresuggested suggested as the as theactive active catalyst, catalyst, and and the involvement of both [Ni(I)–Ni(I)] and [Ni(II)–Ni(II)] intermediates intermediates was was subsequently subsequently suggested suggested [21]. [21]. [(iPrDPDBFphos)NiICl] (iPrDPDBFphos = 4,6-bis(diisopropylphosphinophenyl)dibenzofuran) even

Inorganics 2017,, 5,, 7878 3 of 13

[(iPrDPDBFphos)NiICl] (iPrDPDBFphos = 4,6-bis(diisopropylphosphinophenyl)dibenzofuran) even allowed for the coupling of vinyl chloride and a phenylphenyl GrignardGrignard reagent,reagent, allowing for the incorporation of of a a functional functional group group into into the the target target structure structure and and affording affording styrene styrene in about in about 85% yield 85% yieldwithin within 22 h 22stirring h stirring at room at room temperature temperature [22]. [22 However,]. However, similar similar yields yields were were obtained obtained when when the respective Ni(II) complexcomplex waswas utilizedutilized forfor thethe veryvery samesame reaction.reaction. We recentlyrecently showedshowed thatthatTriphos Triphos (2-((diphenylphosphaneyl)methyl)-2-methylpropane-1,3-diyl)bis (2-((diphenylphosphaneyl)methyl)-2-methylpropane-1,3-diyl)bis Si (diphenylphosphane)- andand TriphosTriphosSi(((methylsilanetriyl)tris(methylene))-tris(diphenylphosphane))- (((methylsilanetriyl)tris(methylene))-tris(diphenylphosphane))- derived Ni Ni and and Fe Fe complexes complexes are are potential potential noble noble metal-free metal-free platforms platforms to conduct to conduct the C–C the cross- C–C cross-couplingcoupling of aryl of iodides aryl iodides and and alkynes [23,24]. [Furthermore,23,24]. Furthermore, the Ni(Triphos) the Ni(Triphos) complexes complexes were shown were to shownstabilize to various stabilize oxidation various states oxidation of Ni states (Scheme of Ni 2) (Scheme [25]. Notably,2)[ 25 ].due Notably, to the high due tosteric the bulk high of steric the bulkTriphos of the ligand, Triphos such ligand, Ni complexes such Ni complexes neither show neither any show disproportionation any disproportionation of the ofrespective the respective Ni(I) Ni(I)complexes complexes to Ni(0) to Ni(0)and Ni(II), and Ni(II), nor do nor they do theyallow allow for dimerization for dimerization to give to givea dinickel a dinickel complex. complex. The Thereported reported reactivity reactivity of such of such Ni(Triphos) Ni(Triphos) complexes complexes pointed pointed our ourattention attention towards towards their their application application for forKumada Kumada cross-coupling cross-coupling reactions. reactions. Since Since Ni(0), Ni(0), Ni(I) Ni(I) and and Ni(II) Ni(II) complexes complexes were were shown shown to to be be reactive complexes and can act as pre-catalysts in the C–C bond coupling reaction under Kumada Kumada conditions, conditions, we herein explore thethe rolerole ofof thethe oxidationoxidation statestate basedbased onon well-definedwell-defined [(Triphos)Ni[(Triphos)NiIICl] for the C–C bond formation by UV/VisUV/Vis and electron paramagn paramagneticetic resonance (EPR) spectroscopy. The data is furthermore supportedsupported byby densitydensity functionalfunctional theorytheory (DFT)(DFT) calculations.calculations.

II IIII IIII Scheme 2. Nickel complexes [(Triphos)Ni[(Triphos)NiCl]Cl] ((11),), [(Triphos)Ni[(Triphos)Ni ClCl22](] (2),), [(Triphos)Ni[(Triphos)Ni Cl](BF44))( (3) and IIII [(Triphos)Ni Cl](ClO4))( (44).).

2. Results and Discussions

I Following aa recently recently reported reported synthetic syntheti route,c route, the Ni(I) the complexNi(I) complex [(Triphos)Ni [(Triphos)NiICl] (1) wasCl] obtained(1) was obtained by reduction of the square-planar complex [(Triphos)NiII IICl2] (2) with cobaltocene in gram by reduction of the square-planar complex [(Triphos)Ni Cl2](2) with cobaltocene in gram scale and goodscale yieldand good (87%). yield The (87%). molecular The structuremolecular of structure1 was previously of 1 was unequivocally previously unequivocally shown by single-crystal shown by X-raysingle-crystal crystallography X-ray crystallography and the monovalent and the electronic monova configurationlent electronic was configur confirmedation by was EPR confirmed spectroscopy, by EPR spectroscopy, as well as its magnetic moment via the Evans method (µ = 1.9 µB) [25]. as well as its magnetic moment via the Evans method (µ = 1.9 µB)[25]. We subsequentlysubsequently investigated investigated the the catalytic catalytic potential potential of complex of complex1 for Kumada-type 1 for Kumada-type cross-coupling cross- reactions.coupling Asreactions. a model As reaction, a model we chosereaction, the couplingwe chose of the para-substituted coupling of para-substituted aryl iodides and phenylmagnesium aryl iodides and bromidephenylmagnesium in THF at room bromide temperature in THF inat theroom presence temper ofature 0.5 mol in the % complexpresence1 .of 0.5 mol % complex 1. Under those conditions, iodobenzene, 4-iodotoluene as well as 4-iodoanisole were successfully coupled to to phenylmagnesium phenylmagnesium bromide bromide and and afforded afforded the the respective respective coupling coupling products products in 89%, in 89%,94% 94%and 86% and 86%yield, yield, respectively respectively (Table (Table 1). 1Likewise,). Likewise, we wewere were able able to toutilize utilize bromobenzene and and 4- 4-bromotoluenebromotoluene with with phenylmagnesium phenylmagnesium bromide, bromide, show showinging that that bromo-substituted bromo-substituted arenes arenes are suitable for the couplingcoupling with complex 1 and cancan bebe usedused insteadinstead ofof thethe usuallyusually expensiveexpensive iodo-derivativesiodo-derivatives (Table1 1).). Here,Here, 1,11,10′-biphenyl and 4-methyl-1,1′0-biphenyl-biphenyl were were obtained obtained in in 91% and 74% isolatedisolated yield, respectively. Following this line, we also testedtested the application of aryl chlorides and fluoridesfluorides as substitutes in the cross-couplingcross-coupling reaction procedure.procedure. However, the respective coupling products were only obtained in 3% and 5% yield at room room temperature, temperature, respectively (Table1 1).). WhenWhen thethe reactionreaction temperature was increased to 60 ◦°C,C, for both aryl chlorideschlorides and fluorides,fluorides, the expectedexpected couplingcoupling product 1,10′-biphenyl was detected via GC–MS analysis in 100% yield startingstarting fromfrom chlorobenzenechlorobenzene and in 44% yield for fluorobenzenefluorobenzene (Table1 1).). Thus,Thus, arylaryl chlorideschlorides andand fluoridesfluorides areare suitablesuitable startingstarting materials at higher temperature for Kumada cross-coupling reactions when complex 1 is applied as potential catalyst, but not at room temperature. Notably, in the absence of complex 1,, nono formationformation of any respective bi-aryl product was observed, highlighting the role of the Ni(I) complex 1 as an

InorganicsInorganics2017, 5, 78 2017, 5, 78 4 of 13 4 of 13 InorganicsInorganics 2017, 5, 78 2017 , 5, 78 4 of 13 4 of 13 Inorganics 2017, 5, 78 4 of 13 important pre-catalyst herein. For the latter case, solely starting material was recovered importantimportant pre-catalyst pre-catalyst herein. herein. For theFor latter the lattercase, solelycase, solelystarting starting material material was recoveredwas recovered of anyimportantquantitatively. respective bi-arylpre-catalyst product herein. was observed,For the highlightinglatter case, thesolely role ofstarting the Ni(I) material complex was1 as recovered an quantitatively.quantitatively. importantquantitatively. pre-catalyst herein. For the latter case, solely starting material was recovered quantitatively. Table 1. Kumada cross-coupling reaction of aryl halides with phenylmagnesium bromide catalyzed Table 1.Table Kumada 1. Kumada cross-coupling cross-coupling reaction reaction of aryl halidesof aryl halideswith phenylmagnesium with phenylmagnesium bromide bromide catalyzed catalyzed Table 1. Kumada cross-coupling[a] reaction of aryl halides with phenylmagnesium bromide catalyzed by Tableby 0.5 1.mol[a] Kumada % 1 . cross-coupling reaction of aryl halides with phenylmagnesium bromide catalyzed by 0.5 molby 0.5%[a] 1 mol . % 1 [a]. 0.5 molby % 10.5 .mol % 1 [a].

YieldYield in in (%) (%) YieldYield in (%) in (%)Yield inYield (%) inYield (%) in (%)Yield in (%) ArylAryl Halide Yield inYield (%) in (%)Yield inYield (%) in (%)Yield inYield (%) in (%)Yield inYield (%) in (%) Aryl HalideAryl Halide Yieldforfor X X =in I= (%) I forYield Xfor = BrX in = Br(%)for X =Yieldfor Cl X in = Cl(%)for X = FYieldfor X in = (%)F Aryl Halide for X = forI X = I for X = forBr X = Brfor X = forCl X = Cl for X = forF X = F [a] [a] [a] [a] for X = I for X = Br 3 [a] ,for 3X =, Cl 3 , [a] for3 X =, F 8989[a] [a] 91 [a]91 [a] 3 , 3 [a], 3 , 3 [a], 89 [a] [a] 91 [a] [a] [c] [a][c] [c] [a][c] 89 91 100 [c] 1003 , 44 [c] 443 , 89 [a] 91 [a] 100 100 [c] 44 44 [c] [c] [c] [a] [a] 100[b] 44 [a] 94 [a] 74 [b] 0 – 94 9494[a] [a] 74 74 [a]74 [a] 0 [b] 0 [b] – – – 94 [a] 74 [a] 0 [b] – 86 [a] – 5 – 86 [a] 86 [a] – – 5 5 – – 8686[a] [a] –– 5 5 – – [a] Reaction conditions: RArI (2.8 mmol), ArMgBr (5.6 mmol), [Ni(I)] (0.5 mol %), THF (6 mL), RT, 2.5 [a] Reaction[a] Reaction conditions: conditions: RArI (2.8 RArI mmol), (2.8 mmol),ArMgBr ArMgBr (5.6 mmol), (5.6 mmol),[Ni(I)] (0.5 [Ni(I)] mol (0.5 %), mol THF %), (6 mL),THF (6RT, mL), 2.5 RT, 2.5 [a] [b] [c] h. ReactionIsolated[b] yields;conditions: Coupling RArI (2.8 product mmol), detected ArMgBr by (5.6 TLC, mmol), but not [Ni(I)] isolated;[c] (0.5 mol Reaction %), THF conditions: (6 mL), RT, RArI 2.5 [a]h. Isolatedh. Isolated yields; yields; Coupling [b] Coupling product product detected detected by TLC, by but TLC, not butisolated; not isolated; Reaction [c] Reaction conditions: conditions: RArI RArI Reactionh.(2.8 Isolated conditions:mmol), yields; ArMgBr RArI [b] Coupling (2.8(5.6mmol), mmol), product ArMgBr [Ni(I)] detected (0.5 (5.6 mmol),mol by %), TLC, [Ni(I)] THF but (6 (0.5 not mL),mol isolated; 60 %), °C, THF [c] 2.5 Reaction (6h. mL),Yield conditions: RT, determined 2.5 h. RArI by Isolated(2.8 mmol),(2.8 yields; mmol),ArMgBr[b] Coupling ArMgBr (5.6 productmmol), (5.6 mmol), detected[Ni(I)] (0.5[Ni(I)] by TLC,mol (0.5 but%), mol notTHFisolated; %), (6 THFmL),[c] (6Reaction60 mL), °C, 2.5 60 conditions: h.°C, Yield 2.5 h. RArIdetermined Yield (2.8 determined mmol), by by (2.8GC–MS mmol), analysis ArMgBr using (5.6 4-methyl-1,1’-bi mmol), [Ni(I)]phenyl (0.5◦ mol as an%), internal THF (6 standard.mL), 60 °C, 2.5 h. Yield determined by ArMgBrGC–MSGC–MS (5.6analysis mmol), analysis using [Ni(I)] 4-methyl-1,1’-bi using (0.5 mol 4-methyl-1,1’-bi %), THFphenyl (6 mL), asphenyl 60an internalC, as 2.5 an h. internal standard. Yield determined standard. by GC–MS analysis using 4-methyl-1,10-biphenyl as an internal standard. GC–MSWhile the analysis coupling using of 4-methyl-1,1’-bi aryl halides andphenyl phenyl as an internalGrignard standard. reagents proceeds rapidly and affords While theWhile coupling the coupling of aryl ofhalides aryl halides and phenyl and phenyl Grignard Grignard reagents reagents proceeds proceeds rapidly rapidly and affords and affords the couplingWhile the products coupling in ofhigh aryl yields, halides we and set outphenyl to explore Grignard the possibilityreagents proceeds to perform rapidly coupling and ofaffords the couplingWhilethe coupling the products coupling products in ofhigh aryl in yields, high halides yields,we andset outwe phenyl setto explore out Grignard to explore the possibility reagents the possibility proceeds to perform to rapidly perform coupling and coupling of affords alkyl of alkyl thehalides coupling and/or products alkyl in highGrignard yields, reagents. we set out Into explorea first the step, possibility we usedto perform phenylethynyl- coupling of alkyland thehalides couplinghalides and/or products and/oralkyl inalkylGrignard high Grignard yields, reagents. we reagents. set In out a to Infirst explore a step,first the westep, possibility usedwe tophenylethynyl-used perform phenylethynyl- coupling and and halidesmethylmagnesium and/or alkyl bromide. Grignard All such reagents. reactions, In however, a first didstep, not yieldwe usedany of phenylethynyl-the desired coupling and ofmethylmagnesium alkylmethylmagnesium halides and/or bromide. alkylbromide. All Grignard such All reactions, such reagents. reactions, however, In however, a did first not step, did yield not we any yield used of anythe phenylethynyl- desiredof the desired coupling and coupling methylmagnesiumproducts, and attempts bromide. to alter All thsuche reaction reactions, conditions however, by did changing not yield temperature, any of the desiredreaction coupling time as methylmagnesiumproducts,products, and attempts and bromide. attempts to alter All to th suchaltere reaction reactions,the reaction conditions however, conditions by did changing notby yieldchanging temperature, any oftemperature, the desiredreaction reaction coupling time as time as products,well as the and catalyst attempts concentration to alter th failede reaction as well conditions in our hands. by changing Likewise, temperature, complex 1 reactioncannot facilitate time as products,well aswell the and catalystas attemptsthe catalyst concentration to alter concentration the failed reaction asfailed conditionswell as in well our by inhands. changing our hands.Likewise, temperature, Likewise, complex reactioncomplex 1 cannot time1 cannotfacilitate as well facilitate wellthe conversion as the catalyst of 1,2-diiodoethane concentration failed and asphenylma well in gnesiumour hands. bromide. Likewise, Neither complex (2-iodoethyl) 1 cannot facilitate asthe the conversion catalystthe conversion concentrationof 1,2-diiodoethane of 1,2-diiodoethane failed asand well phenylma and in our phenylma hands.gnesiumgnesium Likewise, bromide. bromide. complex Neither Neither 1(2-iodoethyl)benzenecannot (2-iodoethyl)benzene facilitate the thenor conversion1,2-diphenylethane of 1,2-diiodoethane were formed and under phenylma our stgnesiumandard bromide.conditions, Neither excluding (2-iodoethyl)benzene alkyliodides for conversionnor 1,2-diphenylethanenor 1,2-diphenylethane of 1,2-diiodoethane were formedwere and phenylmagnesiumformed under underour st andardour bromide. standard conditions, Neither conditions, excluding (2-iodoethyl)benzene excluding alkyliodides alkyliodides norfor for norapplication 1,2-diphenylethane in Kumada cross-couplingwere formed underreactions our wi stthandard the investigated conditions, catalyst.excluding These alkyliodides observations for 1,2-diphenylethaneapplicationapplication in Kumada in were Kumada cross-coupling formed cross-coupling under our reactions standard reactions wi conditions,th the wi investigatedth the excluding investigated catalyst. alkyliodides catalyst. These for observationsThese application observations applicationshow that the in monovalent Kumada cross-coupling Ni complex 1 reactionsis unsuitable with for the the investigated coupling of catalyst.C–C bonds These from observations sp3-centers. inshow Kumada thatshow the cross-coupling that monovalent the monovalent Ni reactions complex Ni complex with 1 is the unsuitable investigated1 is unsuitable for the catalyst. forcoupling the Thesecoupling of C–C observations ofbonds C–C frombonds show sp from3-centers. that sp the3-centers. showA that common the monovalent limitation Ni of complex the Kumada 1 is unsuitable cross-coupling for the couplingreaction ofis3 C–Cthe catalysts’ bonds from low sp 3tolerance-centers. monovalentA commonA Ni common complex limitation limitation1 is of unsuitable the ofKumada the for Kumada the cross-coupling coupling cross-coupling of C–C reaction bonds reaction is from the spcatalysts’is the-centers. catalysts’ low tolerance low tolerance towardsA common functional limitation groups ofwithin the Kumadathe substrate. cross-coupling To investigate reaction the isfunctional the catalysts’ group low tolerance tolerance of towardsAtowards common functional functional limitation groups groups ofwithin the Kumadawithinthe substrate. the cross-coupling substrate. To investigate To reactioninvestigate the isfunctional thethe catalysts’functional group low grouptolerance tolerance tolerance of of towardscomplex functional1 as catalyst, groups we chose within different the substrate. substituted To investigate aryl iodides the and functional also heterocyclic group tolerance iodides asof towardscomplexcomplex functional1 as catalyst, 1 as groupscatalyst, we chose within we differentchose the substrate.different substituted substituted To investigatearyl iodides aryl theiodides and functional also and heterocyclic also group heterocyclic tolerance iodides iodides ofas as complexchallenging 1 as substrates catalyst, wefor chosethe Kumada different coupling substituted (Table aryl 2). iodides Phenyl and iodides also heterocyclicwith additional iodides alkyl, as complexchallengingchallenging1 as substrates catalyst, substrates wefor chosethe for Kumada different the Kumada coupling substituted coupling (Table aryl (Table2). iodides Phenyl 2). andPhenyl iodides also iodides heterocyclicwith additional with iodidesadditional alkyl, as alkyl, challengingalkoxy, aryl andsubstrates fluoride for substituents the Kumada afforded coupling the (Tableexpected 2). couplingPhenyl iodides products with with additional yields between alkyl, challengingalkoxy,alkoxy, aryl substratesand aryl fluoride and for fluoride substituents the Kumada substituents couplingafforded afforded (Tablethe expected2 ).th Phenyle expected coupling iodides coupling products with additionalproducts with yields with alkyl, betweenyields alkoxy, between alkoxy,86% and aryl 94% and (Table fluoride 2, Entries substituents 1–6, 8). Notably,afforded polysubstitutedthe expected coupling aryl iodides products comprising with yields substituents between aryl86% and86% 94% fluoride and (Table 94% substituents 2,(Table Entries 2, Entries 1–6, afforded 8). 1–6, Notably, the 8). expectedNotably, polysubstituted polysubstituted coupling aryl products iodides aryl withiodides comprising yields comprising between substituents substituents 86% 86%in the and ortho 94%-position, (Table 2,for Entries example, 1–6, 2-iodomesitylene 8). Notably, polysubstituted and 1-iodonaphthalene, aryl iodides comprisingdid not show substituents formation andin the 94% orthoin (Tablethe-position, ortho2, Entries-position, for example, 1–6, for 8). example, Notably,2-iodomesitylene 2-iodomesitylene polysubstituted and 1-iodonaphthalene, an aryld 1-iodonaphthalene, iodides comprising did not did show substituents not formation show formation in inof theany ortho coupling-position, product for example, (Table 2, 2-iodomesityleneEntry 7 and 9). These and 1-iodonaphthalene,observations suggest did that not aryl show iodides formation with theof anyortho ofcoupling-position, any coupling product for example,product (Table (Table2, 2-iodomesitylene Entry 2, 7Entry and 9).7 and These and 9). 1-iodonaphthalene, observationsThese observations suggest did suggest that not aryl show that iodides aryl formation iodides with with ofsubstituents any coupling directly product adjacent (Table to 2, iodineEntry 7are and unsu 9). Theseitable observationssubstrates for suggest the cross-coupling that aryl iodides reaction with ofsubstituents anysubstituents coupling directly product directly adjacent (Table adjacent to2 , Entry to iodineare 7 and unsu are 9).itable unsu These substratesitable observations substrates for the suggest for cross-coupling the that cross-coupling aryl iodidesreaction reaction substituentsutilizing complex directly 1, dueadjacent to steric to hindranceiodine are ofunsu theitable oxidative substrates addition for of the the cross-coupling aryl iodide to thereaction Ni(I) withutilizing substituentsutilizing complex complex directly1, due 1to adjacent, duesteric to hindrance steric to iodine hindrance areof the unsuitable oxidativeof the oxidative substrates addition addition forof the cross-couplingarylof the iodide aryl iodideto the reaction Ni(I)to the Ni(I) utilizingcenter. Likewise, complex aryl1, due iodides to steric having hindrance amino, of nitro,the oxidative nitrile, hydroxyl,addition of carbonyl the aryl iodideor carboxylic to the Ni(I)acid utilizingcenter. center.Likewise, complex Likewise, aryl1, due iodides aryl to steric iodides having hindrance having amino, of amino, nitro, the oxidative nitrile,nitro, nitrile,hydroxyl, addition hydroxyl, ofcarbonyl the aryl carbonyl or iodide carboxylic or to carboxylic the Ni(I)acid acid center.groups Likewise,did not allow aryl for iodides successful having C–C amino, bond formationnitro, nitrile, and hydroxyl, resulted incarbonyl decomposition or carboxylic of complex acid center.groupsgroups Likewise,did not did allow aryl not iodides forallow successful for having successful C–C amino, bond C–C nitro, formation bond nitrile, formation hydroxyl, and resulted and carbonyl resulted in decomposition or in carboxylic decomposition acidof complex groups of complex groups1 to a didhitherto not allow unknown for successful product C–C mixture bond formation(Table 2, andEntry resulted 11–17). in decompositionSimilarly, application of complex of did1 to not a1 allowhithertoto a forhitherto successfulunknown unknown C–Cproduct bond product mixture formation mixture (Table and (Table resulted2, Entry 2, in Entry11–17). decomposition 11–17). Similarly, Similarly, of complexapplication application1 to of a of 1heteroaromatic to a hitherto substrates unknown like product iodopyridines mixture (Table (Table 2, Entry2, Entry 18–20) 11–17). did not Similarly, result in theapplication formation of hithertoheteroaromaticheteroaromatic unknown substrates product substrates like mixture iodopyridines like (Table iodopyridines2, Entry(Table 11–17). 2,(Table Entry 2, Similarly, 18–20) Entry 18–20)did application not did result not in ofresult the heteroaromatic formation in the formation of of heteroaromaticthe desired products, substrates neither like iodopyridinesat a higher reaction (Table te2,mperature. Entry 18–20) Most did notlikely, result this in lack the formationof reactivity of substratesthe desiredthe desired like products, iodopyridines products, neither neither (Tableat a higher 2at, Entry a higherreaction 18–20) reaction te didmperature. not temperature. result Most in thelikely, Most formation likely,this lack ofthis of the lack reactivity desired of reactivity thestems desired from anproducts, undesired neither coordination at a higher of the reaction additional temperature. functional Mostgroups likely, with complexthis lack 1of. Thus, reactivity Ni(I) products,stems fromstems neither an from undesired atan a undesired higher coordination reaction coordination temperature.of the additional of the additional Most functional likely, functional this groups lack groups ofwith reactivity complex with complex stems 1. Thus, from 1 .Ni(I) Thus, an Ni(I) stemscomplex from 1 is an only undesired suitable coordination to perform theof the Kumada additional coupling functional of aryl groups Grignard with compounds complex 1. Thus,and alkyl-, Ni(I) undesiredcomplexcomplex 1 is coordination only 1 issuitable only ofsuitable to the perform additional to perform the Kumada functional the Kumada coupling groups coupling of with aryl complex ofGrignard aryl Grignard1 .compounds Thus, compounds Ni(I) and complex alkyl-, and1 alkyl-, complexalkoxy- and 1 is aryl-substitutedonly suitable to performsterically the less-demanding Kumada coupling aryl iodides,of aryl Grignard and has compoundsonly little tolerance and alkyl-, for isalkoxy- onlyalkoxy- suitableand aryl-substituted and to performaryl-substituted the sterically Kumada sterically less-demanding coupling less-demanding of aryl aryl Grignard iodides, aryl iodides, compoundsand has and only has and little only alkyl-, tolerance little alkoxy- tolerance for for alkoxy-other functional and aryl-substituted groups. sterically less-demanding aryl iodides, and has only little tolerance for andother aryl-substituted functionalother functional groups. sterically groups. less-demanding aryl iodides, and has only little tolerance for other functionalother groups. functional groups.

InorganicsInorganics 2017, 5, 78 5 of 13 Inorganics 2017, 5, 78 5 of 13 InorganicsInorganics 2017,, 5,, 7878 Inorganics 2017, 5, 78 5 of 13 5 of 13 InorganicsInorganics 2017 2017,, ,5 5,, ,7878 78 InorganicsInorganics 20172017,,, 55,,, 787878 55 of of 13 13 55 ofof 1313 InorganicsInorganics 2017,, 5,, 7878 Inorganics 2017,, 5,, 7878 5 of 13 5 of 13 InorganicsTable 20172. Kumada, 5, 78 InorganicsInorganicsTable cross-coupling 2. 20172017 Kumada,, 55,, 7878 cross-coupling reaction of reaction aryl iodides of aryl iodideswith phenylmagnesium with phenylmagnesium bromide5 of bromide 13 catalyzedcatalyzed55 ofof 1313 TableTable 2. 2.Kumada KumadaKumada cross-couplingcross-coupling Table 2. Kumada reactionreactionreaction cross-coupling ofof arylaryl of iodidesiodides aryl reaction iodideswithwith ofphenylmagnesiumphenylmagnesium aryl with iodides phenylmagnesium with bromide bromidephenylmagnesium catalyzedcatalyzed bromide bromide catalyzed catalyzed by by 0.5TableTable mol 2. 2. Kumada Kumada Kumada% 1 [a]by. cross-coupling cross-couplingcross-coupling 0.5TableTable mol 2.2. % KumadaKumadaKumada 1 [a] reaction reaction.reaction cross-couplingcross-couplingcross-coupling of ofof aryl arylaryl iodides iodidesiodides reactionreactionreaction with withwith ofofofphenylmagnesium phenylmagnesiumphenylmagnesium arylarylaryl iodidesiodidesiodides withwithwith bromidebromide phenylmagnesiumbromidephenylmagnesiumphenylmagnesium catalyzed catalyzedcatalyzed bromidebromidebromide catalyzedcatalyzedcatalyzed Table 2. Kumada[a] cross-couplingTable 2. KumadaKumada reaction[a] cross-couplingcross-coupling of aryl iodides reactionreaction with ofofphenylmagnesium arylaryl iodidesiodides withwith bromide phenylmagnesiumphenylmagnesium catalyzed bromidebromide catalyzedcatalyzed Tableby 0.5 mol2. KumadaKumada %[a] 1 [a][a]. cross-couplingcross-couplingbyTable 0.5 mol2. Kumada % reactionreaction1 . cross-coupling ofof arylaryl iodidesiodides reaction withwith ofphenylmagnesiumphenylmagnesium aryl iodides with bromidebromide phenylmagnesium catalyzedcatalyzed bromide catalyzed 0.5by molby 0.50.5 % molmol1 %% 11. [a] [a]. . Table 2. Kumada[a][a][a] cross-coupling reaction of aryl iodides with phenylmagnesium bromide catalyzed byTable 0.5 mol2. Kumada % 1 [a].. cross-couplingbybyTable 0.50.5 molmol2. Kumada %% 1reaction1 [a][a]... cross-coupling of aryl iodides reaction with ofphenylmagnesium aryl iodides with bromide phenylmagnesium catalyzed bromide catalyzed by 0.5 mol % 1 [a][a]. by 0.5 mol % 1 [a]. by 0.5 mol % 1 .. by 0.5 mol % 1 [a] . [a] byby 0.50.5 molmol %% 11 [a].. I by 0.5 mol % 1 . I 0.5 mol-%I [Ni ] 0.5 mol-% [NiI]I I I 0.5+0.5 mol-%mol-%0.5 [Ni[NiMgBrII ]mol-%] 0.5 [Ni mol-%] [NiIII] I + MgBr 0.5+ mol-% [NiI] 0.50.5 mol-%mol-% [Ni[NiII]] II ++I + MgBrMgBr 0.5IMgBr +THF,mol-% rt, [Ni II]MgBr 0.5THF, mol-% rt, [NiI] R II + R MgBr 0.5II ++ mol-%THF,THF, rt,rt, [Ni I]MgBrTHF,MgBrR 0.50.5rt, mol-%THF,mol-% rt, [Ni[Ni I]I] R RR II + R MgBr 0.5I + THF,mol-%2.5h rt, [Ni ]MgBrRR 0.5 THF,THF,mol-%2.5h rt,rt, [Ni ] R RR I + RR MgBr II ++THF,2.5h2.5h rt, MgBrMgBrR THF,2.5h Rrt, RR R R THF,2.5h rt, R2.5h THF,THF,2.5h2.5h rt,rt, R R RR 2.5h R 2.5h RR [b]2.5h [b]2.5h 2.5h [b] [b] Entry EntryProduct ProductYield (%) [b][b] EntryYield [b](%) [b] Product Entry Yield Product (%) [b][b] Yield (%)[b] [b] EntryEntry EntryProductProduct Product ProductYieldYield (%)(%)[b][b] YieldEntryEntry (%)Yield (%) [b][b][b] Product Product Entry Entry YieldYield Product (%)(%)[b][b] YieldYield (%) (%)[b][b][b] Entry EntryEntryProduct ProductProductYield (%) [b] EntryYieldYield (%)(%) [b] Product[b] EntryEntry Yield Product Product (%) [b] YieldYield (%)(%) [b][b] Entry EntryProduct ProductYield (%) [b][b] EntryYield[b] (%) Product[b] Entry Yield Product (%) [b][b] Yield (%) [b] [b] EntryEntry EntryProductProduct ProductYield (%)Yield (%)EntryYield (%)Entry[b] Product Entry ProductYield Product (%) YieldYield (%) (%)[b] Entry1 1 EntryEntryProduct1 P1 ProductProductYield89 (%) [b] P1P1 Entry 11 YieldYield8989 (%)(%) Product[b] EntryEntry 11 11 Yield Product Product0 (%) [b] YieldYield 0 (%)(%)0 [b] 11 11 P1P1 8989 P1P1 11 11 8989 11 11 00 00 11 1 P1 P1 89 P1 11 89 89 11 11 0 0 0 1 1 11 P1 P1 89 89P1P1 11 8989 11 11 11 0 00 0 1 1 P1 89 P1 11 89 11 0 0 2 2 2 P2 94 P2P2 12 9494 12 12 0 00 22 22 P2P2 9494 P2P2 12 12 9494 12 12 00 00 2 2 P2 94 P2 12 94 12 0 0 22 2 P2 P294 P2 12 94 94 12 12 0 0 0 2 2 2 P2 P2 94 94P2 12 94 12 12 0 0 0

3 3 P3 86 P3 13 86 13 0 0 33 3 33 P3P3 8686 P3P3P3 13 13 868686 13 13 13 00 00 0 33 3 P3 P386 P3 13 86 86 13 13 0 0 0 3 33 P3 86 P3P3 13 8686 13 13 0 00 3 3 P3 86 P3 13 86 13 0 0

3 P3 86 13 0 4 P4 92 14 0 44 4 4 P4P4 P49292 P4P4 14 14 92 9292 14 14 14 00 00 0 4 44 P4 92 P4P4 14 9292 14 14 0 00 4 4 P4 92 P4 14 92 14 0 0 4 44 P4 92 P4P4 14 9292 14 14 0 00

55 5 P5P5 P57575 P5 15 15 75 75 15 15 00 0 0 4 5 5 55 P5 P4 75 P592P5P5 15 757575 14 15 15 15 0 00 0 0 5 5 P5 75 P5 15 75 15 0 0 5 55 P5 75 P5P5 15 7575 15 15 0 00

66 6 P6 P696 P6 16 96 96 16 16 0 0 0 66 66 P6P6 9696 P6P6 16 16 9696 16 16 00 00 6 6 6 P6 96 P6P6 16 9696 16 16 0 00 5 6 66 P6 P5 96 75P6P6 16 9696 15 16 16 0 00 0 6 6 P6 96 P6 16 96 16 0 0

7 7 17 17 17 0 0 77 77 17 17 17 17 00 00 77 7 7 17 17 17 17 17 17 0 00 0 7 7 17 17 17 0 0 6 7 77 P6 96 17 16 17 17 0 00 0

8 8 P7 97 P7 18 97 18 0 0 88 88 P7P7 9797 P7P7 18 18 9797 18 18 00 00 88 8 8 P7 P797 P7P7 18 97 9797 18 18 18 0 00 0 8 88 P7 97 P7P7 18 9797 18 18 0 00

7 17 0 9 9 00 19 19 0 19 0 0 99 99 000 19 19 19 000 19 19 19 00 00 9 9 00 19 19 00 19 19 0 0 99 9 9 0 19 000 19 19 19 0 0 0 0 9 9 0 19 0 19 0 0

10 10 0 20 0 20 0 0 1010 10 000 20 20 20 0 20 00 0 10 1010 00 20 20 000 20 20 20 0 00 8 10 10 P7 00 97 20 20 0 18 20 0 0 0 [a]1010 10 1010 0 20 000 0 20 20 20 20 0 00 0 0 [a][a] Reaction conditions:[a] RArI (2.8 mmol), ArMgBr (5.6 mmol), [Ni(I)] (0.5 mol %), THF (6 mL), RT, [a][a] ReactionReaction conditions:conditions:[a][a][a] Reaction RArIRArI (2.8(2.8 conditions: mmol),mmol), ArMgBrArMgBr RArI (2.8 (5.6(5.6 mmol), mmol),mmol), ArMgBr [Ni(I)][Ni(I)] (0.5(5.6(0.5 molmolmmol), %),%), [Ni(I)]THFTHF (6(6 (0.5 mL),mL), mol RT,RT, %), THF (6 mL), RT, [a] ReactionReaction conditions:conditions:[a][a] ReactionReactionReaction RArIRArI (2.8(2.8 conditions:conditions:conditions: mmol),mmol), ArMgBrArMgBr RArIRArIRArI (2.8(2.8(2.8 (5.6(5.6 mmol),mmol),mmol), mmol),mmol), ArMgBrArMgBrArMgBr [Ni(I)][Ni(I)] (0.5 (0.5(5.6(5.6(5.6 mol molmmol),mmol),mmol), %),%), [Ni(I)]THF[Ni(I)]THF[Ni(I)] (6(6 (0.5(0.5 (0.5 mL),mL), molmolmol RT,RT, %),%),%), THFTHFTHF (6(6(6 mL),mL),mL), RT,RT,RT, [a][a] Reaction[b] conditions:[a] ReactionReaction RArI[b] (2.8 conditions:conditions: mmol), ArMgBr RArIRArI (2.8(2.8 (5.6 mmol),mmol), mmol), ArMgBrArMgBr [Ni(I)] (0.5 (5.6(5.6 mol mmol),mmol), %), THF[Ni(I)][Ni(I)] (6 (0.5 (0.5mL), molmol RT, %),%), THFTHF (6(6 mL),mL), RT,RT, 2.5 ReactionReaction h; [b][b] Isolated conditions:conditions: [a]yields.[a] Reaction RArIRArI (2.8(2.8 conditions: mmol),mmol), ArMgBrArMgBr RArI (2.8 (5.6(5.6 mmol), mmol),mmol), ArMgBr [Ni(I)][Ni(I)] (0.5(0.5(5.6 mol molmmol), %),%), THF[Ni(I)]THF (6(6 (0.5 mL),mL), mol RT,RT, %), THF (6 mL), RT, [a]2.52.5 h;h; [b] [b] IsolatedIsolated yields.yields.2.5[a] Reaction h; [b][b][b] Isolated conditions: yields. RArI (2.8 mmol), ArMgBr (5.6 mmol), [Ni(I)] (0.5 mol %), THF (6 mL), RT, 2.5 Reaction h; [b] IsolatedIsolated conditions: yields.yields. Reaction2.52.5 Reaction h;h;RArI [b][b] IsolatedIsolatedIsolatedconditions: (2.8 conditions: mmol), yields.yields.yields. RArIArMgBr RArI (2.8 (2.8 (5.6mmol), mmol), mmol), ArMgBr ArMgBr [Ni(I)] (5.6(0.5 (5.6 mmol),mol mmol), %), [Ni(I)] THF[Ni(I)] (6 (0.5 (0.5mL), molmol RT, %), THFTHF (6(6 mL),mL), RT, RT, 2.5 h; [b][b] IsolatedIsolated yields.yields.2.5 h; [b] IsolatedIsolated yields.yields. [a] Reaction2.5 h; [b] Isolated conditions: yields.2.52.5[b] h;h; RArI [b][b] IsolatedIsolated (2.8 yields.yields. mmol), ArMgBr (5.6 mmol), [Ni(I)] (0.5 mol %), THF (6 mL), RT, 2.5 h; Since2.5Since h; complexes complexes Isolated 2.5yields. featuring featuringh;Since Isolated complexes a a Ni(II) Ni(II) yields. ion ionfeaturing were were also also a Ni(II) reported reported ion were for for catalyzing catalyzingalso reported Kumada Kumada for catalyzing cross-coupling cross-coupling Kumada cross-coupling [b]9 Since complexes featuringSinceSince complexescomplexes a Ni(II) ion featuringfeaturing were also aa Ni(II)Ni(II) reported 0ionion werewere for catalyzing alsoalso 19reportedreported Kumada forfor catalyzingcatalyzing cross-coupling KumadaKumada cross-couplingcross-coupling0 reactions,IsolatedSince wecomplexes yields. nextreactions, tested featuringSince the wecomplexes Ni(II) a next Ni(II) complexes tested ion featuring were the 2alsoNi(II)– a4 Ni(II) (1 (1reported complexesandand ion 0.50.5 were for molmol catalyzing 2also – %%4 (1 catalystcatalystreported and Kumada 0.5 loading)loading) for mol catalyzing cross-coupling% asascatalyst potentialpotential Kumada loading) cross-coupling as potential reactions,reactions,Since wecomplexeswe nextnextreactions,reactions, testedSincetested featuringSinceSince complexes thethe we complexeswecomplexes Ni(II)Ni(II) a nextnext Ni(II) complexes featuringcomplexestestedtested ion featuringfeaturing were thethe a 2Ni(II)Ni(II)also2 –Ni(II) a–a4 4 Ni(II) Ni(II) (1 (1reported complexes complexesand andion ionion were0.50.5 werewere for molmol also catalyzing 2 2alsoalso– – %4%4 reported(1 (1catalyst reportedcatalystreported andand Kumada 0.50.5 loading) forloading) for for molmol catalyzing catalyzing cross-coupling%% ascatalystcatalystas potentialpotential KumadaKumada loading)loading) cross-coupling cross-couplingcross-coupling asas potentialpotential reactions,catalysts inwe our next modelreactions, tested reaction, the we Ni(II) next namely complexes tested thethe 2couplingNi(II)–4 (1(1 complexesandand of 0.50.5 4-iodotoluene molmol 2 –%%4 (1catalystcatalyst and and 0.5 loading)loading) phenylmagnesiummol % asascatalyst potentialpotential loading) as potential reactions,catalystscatalysts ininwe our ournext modelreactions,catalystsmodelreactions, tested reaction, reaction,the in wewe Ni(II)our nextnext namely namely model complexes testedtested reaction, thethethe 2Ni(II)couplingNi(II)coupling–4 (1namely complexesandcomplexes ofof 0.5 4-iodotoluenethe4-iodotoluene mol 2coupling2– –%44 (1(1catalyst andand ofand and 0.50.5 loading)4-iodotoluene molphenylmagnesiummolphenylmagnesium %% ascatalystcatalyst potential and loading)loading) phenylmagnesium asas potentialpotential catalysts in ourreactions, modelcatalystscatalysts reaction,we inin next ourour testednamelymodelmodel the reaction,reaction,the Ni(II) coupling complexesnamelynamely of 4-iodotoluenethethe 2 –couplingcoupling4 (1 and of andof0.5 4-iodotoluene4-iodotoluene molphenylmagnesium % catalyst andand loading) phenylmagnesiumphenylmagnesium as potential catalystsbromide underin our otherwise modelbromidecatalysts reaction, identical underin our otherwise namely modelconditio reaction,the nsidentical ascoupling applied namely conditio of above. 4-iodotoluenethens asNi(II)coupling applied complex andofabove. 4-iodotoluene phenylmagnesium2 waswasNi(II) obtainedobtained complex and inin phenylmagnesium2 was obtained in bromidecatalystsbromideSince complexes underinunder ourcatalysts otherwise otherwisemodelcatalystsbromidebromidecatalysts featuring inreaction, identical underidenticalunderinourin ourour model otherwise otherwise namely a modelmodel conditioconditio Ni(II) reaction, reaction,reaction,the nsidenticalns ionidentical ascouplingas were appliedappliednamely namelynamely conditioconditio also of above. above. the 4-iodotoluenethethens reportedns coupling asascoupling Ni(II)couplingNi(II) appliedapplied complexcomplex for ofof andofabove.above. catalyzing4-iodotoluene4-iodotoluene4-iodotoluene phenylmagnesium 22 wasNi(II)wasNi(II) obtainedobtained complexcomplex Kumada andand in in phenylmagnesium phenylmagnesium2phenylmagnesium 2 waswas cross-coupling obtainedobtained inin bromide94%10 yield under according otherwisebromide to literature-known identicalunder otherwise conditio proced nsidentical asures applied conditioby0 complexation above.ns asNi(II) applied 20 complexof Triphos above. 2 waswaswithNi(II) obtainedobtained NiCl complex2, and inin 2 was obtained0 in bromide94% yield under according otherwisebromide94% to yield literature-known identicalunder according otherwise conditio to procedliterature-known nsidentical as uresapplied conditioby complexationabove. procedns asNi(II) uresapplied complexofby Triphos complexationabove. 2 wasNi(II)with obtained NiClcomplexof Triphos22, and in 2 waswith obtained NiCl2, and in 94%bromide94% yieldyield under accordingaccording otherwise94%94%bromide to to yieldyield literature-knownliterature-known identical under accordingaccording otherwise conditio toto procedliterature-knownliterature-knownproced nsidentical asures uresapplied conditiobyby complexationcomplexationabove. procedprocedns asNi(II)uresures applied complexofbybyof Triphos Triphoscomplexation complexationabove. 2 waswithNi(II)with obtained NiCl NiClofcomplexof TriphosTriphos2, , andand in 2 waswithwith obtained NiClNiCl22,, andand in 94% yield accordingbromide94% to yield underliterature-known according otherwise to identicalprocedliterature-knownures conditio by complexation procedns as appliedures ofby Triphosabove.complexation Ni(II)with NiCl complexof Triphos2, and 2 withwas obtainedNiCl2, and in reactions,94%Ni(II) yield complexes we according next 94%3 tested andto yield literature-known 4 thewereaccording Ni(II) formed to complexes proced literature-knownvia reactionures by2 –ofcomplexation4 proced[Ni(CH(1 andures3CN) 0.5 ofby6](BF) molTriphoscomplexation2 or % with catalystNi(ClO NiCl of4)·6H Triphos2,, loading) and2O, with asNiCl potential2, and 94%Ni(II) yield complexes according 94%Ni(II)3 andto yield literature-knowncomplexes 4 accordingwere formed 3 andto procedliterature-known via4 were reactionures formed by ofcomplexation proced [Ni(CHvia reactionures33CN) ofby66](BF) Triphosofcomplexation [Ni(CH22 or withNi(ClO3CN) NiClof64](BF) 4)·6HTriphos, and22O, or withNi(ClO NiCl4)·6H2, and2O, Ni(II)94%Ni(II) yield complexescomplexes according Ni(II) Ni(II)94%33 andtoand yield literature-knowncomplexes complexes 44 wereaccordingwere formed formed33 andandto proced literature-known via4via4 were were reactionreactionures formedformed by ofcomplexationof proced[Ni(CH[Ni(CHviavia reactionreactionures3CN)CN) ofby6](BF) ](BF)Triphos ofofcomplexation [Ni(CH2[Ni(CH oror withNi(ClONi(ClO33CN)CN) NiCl of664](BF)](BF))·6H )·6HTriphos2, and22O, O,oror withNi(ClONi(ClO NiCl44)·6H)·6H2, and22O,O, Ni(II)[a] complexes94% Ni(II) 3yield andand complexes according4 werewere formedformed 3to andliterature-known viavia4 werereactionreaction formed ofof proced [Ni(CH[Ni(CHvia uresreaction3CN) by6](BF)](BF) complexationof 2[Ni(CH oror Ni(ClONi(ClO3CN) of64](BF))·6H )·6HTriphos22O, or withNi(ClO NiCl4)·6H2, 2andO, Ni(II)respectively, Reaction complexes to conditions: the respectively,Ni(II)3 Ni(II) and complexes complex4 RArIwere to the 2(2.8formed [23,25].[23,25]. 3Ni(II) andmmol), complexvia4 were reactionArMgBr 2formed [23,25]. of (5.6 [Ni(CH via mmol), reaction3CN) 6[Ni(I)]](BF) of 2[Ni(CH or(0.5 Ni(ClO mol3CN) 64%),](BF))·6H THF22O, or (6Ni(ClO mL),4)·6H RT,2O, catalystsrespectively,Ni(II)respectively, incomplexes our to tomodel the the Ni(II)respectively,Ni(II) 3Ni(II) Ni(II)and reaction, complexes complexescomplex complex4 were to the2 namely2formed [23,25]. 3[23,25]. 3Ni(II) andand complexvia 44 the were werereaction coupling 2formedformed [23,25]. of of[Ni(CH viavia 4-iodotoluene reactionreaction3CN)6](BF) ofof [Ni(CH2[Ni(CH or and Ni(ClO33CN)CN) phenylmagnesium664](BF)](BF))·6H22O, oror Ni(ClONi(ClO44)·6H)·6H bromide22O,O, respectively, toNi(II) therespectively,respectively, Ni(II) complexes complex toto thethe 32 [23,25].[23,25].and Ni(II)Ni(II) 4 complex complexwere formed 2 [23,25].[23,25]. via reaction of [Ni(CH3CN)6](BF)2 or Ni(ClO4)·6H2O, respectively,2.5 Anh; [b]overview Isolated to the respectively,of Ni(II) yields. theAn observedcomplex overview to the 2product [23,25].[23,25].of Ni(II) the observed yields complex is provided2product [23,25]. yieldsin Table is provided3. Yields givenin Table for 3. 4-methyl- Yields given for 4-methyl- underrespectively, otherwiseAnAn overviewoverview to the identicalrespectively, respectively, of ofNi(II) thetheAnAn observedcomplexobserved overviewoverview conditions toto thethe 2 productproduct [23,25].of of Ni(II)Ni(II) thethe observed observedascomplex yieldscomplexyields applied isis provided2product2providedproduct [23,25].[23,25]. above. yields yields inin TableTable Ni(II) isis provided provided 3.3. YieldsYields complex in giveningiven TableTable 2 forforwas 3.3. 4-methyl- 4-methyl- YieldsYields obtained givengiven forfor in 4-methyl-4-methyl- 94% yield 1,1′-biphenylAn overview wererespectively, of determined theAn observed overview to the by Ni(II)product GC–MS of the complex observedyields analysis is 2 provided[23,25]. productusing 1,1 yieldsin′-biphenyl Table is provided3. Yieldsas an giveninternalin Table for calibration3. 4-methyl- Yields given for 4-methyl- 1,11,1′′-biphenyl-biphenylAn overview werewere 1,1of determineddetermined ′the-biphenylAnAn observed overviewoverview were byby product GC–MS ofGC–MSof determined thethe observedobservedyields analysisanalysis isby provided product product usingGC–MSusing 1,11,1 yields yieldsinanalysis′′-biphenyl-biphenyl Table isis provided provided 3.using Yields asas an an1,1 ingiveninternalin′internal-biphenyl TableTable for 3.calibration3. calibration4-methyl- YieldsYieldsas an giveninternalgiven forfor calibration 4-methyl-4-methyl- according1,1′′-biphenyl-biphenyl to literature-known werewere1,11,1 determineddetermined′′′-biphenyl-biphenyl werewerebyby procedures GC–MSGC–MS determineddetermined analysisanalysis by byby complexation usingusingGC–MSGC–MS 1,11,1 analysisanalysis′′-biphenyl-biphenyl of Triphosusingusing asas an an 1,11,1 internalinternal′′′-biphenyl with-biphenyl NiCl calibrationcalibration asas ,anan and internalinternal Ni(II) calibrationcalibration complexes 1,1standard.Since′′-biphenyl-biphenyl complexes In werewereaddition,standard.1,1 Andetermineddetermined′′-biphenyl featuringoverview isolated In werebybyaddition, ofyields a GC–MS GC–MS theNi(II) determined observed fromisolated analysisionanalysis experiments were by productyields usingusingGC–MS also fromyields1,11,1 applying reportedanalysis′′-biphenyl-biphenyl experiments is provided usingcomplex forasas anan catalyzing1,1 applyingininternalinternal ′′-biphenyl 1Table areare calibration3.addedcalibrationaddedcomplex YieldsKumadaas2 an forfor internal given 1 arecross-coupling for addedcalibration 4-methyl- for standard.1,1standard.′-biphenyl InIn wereaddition,addition,1,1standard.standard.1,1 determined′′-biphenyl-biphenyl isolatedisolated InIn werewereaddition,byaddition, yieldsyields GC–MS determineddetermined from fromisolatedisolated analysis experimentsexperiments by by yieldsyields usingGC–MSGC–MS fromfrom1,1 applying applyinganalysisanalysis′-biphenyl experimentsexperiments usingusingcomplexcomplex as an 1,1 1,1 applyingapplyinginternal ′ ′-biphenyl-biphenyl11 areare addedcalibrationaddedcomplexcomplex asas anan for for internal internal 11 areare calibrationaddedaddedcalibration forfor 3 standard.comparison.4 In While1,1addition,′-biphenylstandard. application isolated wereIn addition, ofyields determined complex from isolated 2 experimentsbygenerally GC–MSyields leadsfrom analysisapplying experimentsto a usingcompletecomplex 1,1 applying′ -biphenyl ·1conversion areare addedaddedcomplex as ofan forfor4- internal 1 are addedcalibration for reactions,andstandard.comparison.comparison.were we In formed nextWhileWhileaddition,standard.comparison.standard. tested applicationapplication via isolated reaction theInIn While addition, addition,Ni(II)ofofyields complexcomplex ofapplication [Ni(CH complexesfrom isolatedisolated 22 experiments generallygenerally 3 ofCN)yieldsyields complex26– ](BF) 4 fromleadsfrom leads (1applying 2and experimentsexperimentstoortogenerally a Ni(ClOa0.5 completecomplexcomplete mol leads 4applyingapplying ) % 16Hconversion conversion tocatalystare2 O,a addedcomplexcompletecomplex respectively, ofloading)of for 4- 4- 11conversion areare asadded toadded thepotential of for Ni(II)for4- comparison. Whilecomparison.comparison. application WhileWhile of complex applicationapplication 2 generallygenerally ofof complexcomplex leadsleads 2 2 totogenerallygenerally aa completecomplete leadsleads conversionconversion toto aa completecomplete ofof 4-4- conversionconversion ofof 4-4- comparison.iodotolueneiodotoluene totoWhilestandard. thetheiodotoluenecomparison. desireddesired application In couplingcoupling addition, toWhile theof productproductcomplexdesired applicationisolated forcouplingfor 2 bothboth generallygenerallyyields of 11 product complexandand from leadsleads0.50.5 for mol molexperiments2 totoboth generally %% aa catalystcatalyst 1completecomplete and leads 0.5 loading,loading,applying molconversionconversion to % formationformationa catalyst completecomplex ofof loading, of4-of4- conversion1 are formation added of of4-for catalystscomplexiodotoluenecomparison.iodotoluene 2in[23 our to,to25While thethe ].modelcomparison.iodotolueneiodotoluene comparison. desireddesired application couplingreaction,coupling to toWhileWhile thetheof product complexdesiredproductdesired applicationapplicationnamely coupling forcoupling for2 both generallyboth the ofof 1 1product productcomplex complex andcouplingand leads 0.50.5 forfor mol mol22 tobothbothgenerally generally % %ofa catalyst catalyst 11complete4-iodotoluene andand leads0.5 leads0.5 loading,loading, molmolconversion toto %% formationa a formationcatalystcatalyst complete completeand of loading,loading, of4-phenylmagnesiumof conversion conversion formationformation ofof of4-of4- iodotoluene4-methyl-1,1iodotoluene ′toto-biphenylcomparison. thetheiodotoluene desireddesired was couplingcoupling observedWhile to the applicationproduct product desiredin solely forforcoupling 72% bothbothof (1 complex 1mol1 product andand %) 0.50.5 and formol2mol 46%generally both %% catalystcatalyst(0.5 1 and mol leads 0.5 loading,loading, %), mol asto well% formationaformation catalyst complete as 59% loading, ofof(1 conversion formation of of4- iodotoluene4-methyl-1,14-methyl-1,1 to′′-biphenyl-biphenyl theiodotoluene4-methyl-1,1 iodotoluenedesired waswas coupling observedobserved to′to-biphenyl thethe product desired desired inin solelysolely was couplingforcoupling observed 72%72% both (1(1 1 mol productmolproduct andin solely %)%) 0.5 andand formolfor 72% 46% both46%both % (1 catalyst (0.5 (0.5 1mol1 andand molmol %) 0.5 0.5loading, %),and%), molmol as as46% % well%well formation catalystcatalyst(0.5 asas mol 59%59% loading, loading, %), of (1(1 as well formationformation as 59% of(1of bromide4-methyl-1,1An overviewunder′′-biphenyl-biphenyl otherwise4-methyl-1,14-methyl-1,1 ofthe waswas observed observedobserved identical′′′-biphenyl-biphenyl inin product solelysolely conditiowaswas observed observed 72%72% yields (1(1ns molmol asinin solely%)solely%)applied is andand provided 72%72% 46%46% (1(1above. (0.5(0.5 molmol mol inmol %)%) Table Ni(II) %),%),andand asas 46%46%3 wellwell .complex Yields(0.5(0.5 asas mol mol59%59% given%), %), (1(12 aswasas wellwell for obtained asas 4-methyl- 59%59% (1(1 in 4-methyl-1,1mol %) and 41%′′-biphenyl-biphenyliodotoluene (0.5mol4-methyl-1,1 mol %) waswas %),and toobservedobserved yields 41%the′′-biphenyl desired (0.5 for inin molcomplexes solelysolely was coupling %), observed 72%72% yields 3 (1(1 and andproduct molformol in 4 complexes, , %) solely%)respectively.respectively. andandfor 72% both 46%46% 3 (1 and (0.5(0.51 However,molHowever, and 4molmol, %) respectively.0.5 %),%),and mol whilewhile asas 46% %wellwell catalystthethe(0.5 However, asas amountamount mol59%59% loading, %), (1(1 while as well formationthe as amount 59% (1 of 0 mol4-methyl-1,1mol %) %) and and 41% ′41%-biphenyl (0.5 (0.54-methyl-1,1molmol4-methyl-1,1 mol mol %) %)was %),andand%), observed yields yields41%41%′′-biphenyl-biphenyl (0.5(0.5 for for in molcomplexesmol complexessolely waswas %),%), observed observed 72% yieldsyields 3 3(1 and and formolfor in in4 4complexescomplexes , solely ,%)solelyrespectively. respectively. and 72%72% 46% 33 (1 (1and and(0.5 molHowever, molHowever, 44mol0, , %) %)respectively.respectively. %),andand while whileas 46%46% well the(0.5(0.5the However,However, as amount molamount mol59% %), %),(1 whilewhile asas wellwell thethe asas amountamount 59%59% (1(1 1,1 -biphenylmolof 4-methyl-1,1 %) and 41% were′-biphenyl (0.5mol determinedmol %) %), formedand yields 41% is (0.5 loweredfor by molcomplexes GC–MS %), for yields3 and 3 analysisandand 4 for, the 4 complexes,, respectively.respectively.results using clearly 3 and 1,1However,However, show 4,-biphenyl respectively. that whilewhile Ni(II) thethe ascomplexes However, amountamount an internal while the calibration amount2 94%molof ofyield 4-methyl-1,14-methyl-1,1 %) and according 41%4-methyl-1,1′′-biphenyl-biphenyl (0.5molofmol 4-methyl-1,1mol %)to%) %),and formedandformedliterature-known′-biphenyl yields 41%41% ′ is-biphenylis (0.5 (0.5lowered forlowered wasmolcomplexesmol %),observedformed%), forfor yields yields3 3 proced andand 3 isand 4 loweredfor4infor,, the the4 solely complexescomplexes,ures respectively. resultsresults for 72% by 3 clearly clearlyand 3(13complexation and andmol 4However,, showthe show 44 ,%), respectively. respectively.results and thatthat while Ni(II)46% Ni(II)clearly of the(0.5 complexesHowever,complexesHowever,Triphos show amount mol that %), while while Ni(II)aswith well thethe complexes NiCl as amountamount 59%, and(1 of 4-methyl-1,1′′-biphenyl-biphenylofof 4-methyl-1,14-methyl-1,1 formedformed ′ ′′is-biphenylis-biphenyl loweredlowered formed formed forfor 3 andand isis 4loweredlowered,, thethe resultsresults forfor 3 3 clearlyclearly andand 44,, showshowthethe resultsresults thatthat Ni(II)Ni(II) clearlyclearly complexescomplexes showshow thatthat Ni(II)Ni(II) complexescomplexes standard.ofcan 4-methyl-1,1 likewise In addition, bemol′′ -biphenyl-biphenylutilizedcanof %) 4-methyl-1,1 likewiseand isolated as formedformed 41%potential be (0.5 ′′isis -biphenylyieldsutilized loweredlowered molpre-cata %), fromas formed forfor lystslystsyieldspotential 3 experiments andand forfor isfor 4loweredthethe ,,pre-cata thethecomplexes KumadaKumada resultsresults forlysts applying 3 clearly clearly reaction, reaction,and3 for and 4the, show showthe4, Kumadarespectively.withwithcomplex results thatthat complexescomplexes Ni(II)Ni(II) clearlyreaction,1 complexescomplexesareHowever, show 1 withand addedand that 2complexes while Ni(II) for comparison.thecomplexes 1 amount and 2 Ni(II)canofcan 4-methyl-1,1 complexes likewiselikewise bebe′ -biphenyl utilizedutilized ofcancanof3 4-methyl-1,1 4-methyl-1,1 likewiseandlikewise asas formed potentialpotential4 bebewere′ ′ -biphenylis -biphenylutilizedutilized lowered pre-catapre-cata formed asas formed formedfor lystspotentialpotentiallysts 3 and forfor via isis 4lowered thelowered the,pre-cata pre-cata thereaction KumadaKumada results forforlystslysts 3 3 clearly reaction, andand reaction, forforof 44thethe,[Ni(CH, show thethe KumadaKumada with with resultsresults that complexescomplexes3 CN)Ni(II) clearly clearlyreaction,reaction,6 ](BF)complexes showshow 11 withwith andand2 thatthator 2 complexes2complexes Ni(II)Ni(II)Ni(ClO complexescomplexes 11 4 andand)·6H 22 2 O, canshowing likewise the highestbe utilizedcan amounts likewise as potential of be isolated utilized pre-cata product. as lystslystspotential Heforfor re, thethe pre-cata the KumadaKumada choicelysts ofreaction,reaction, for the the counterions Kumadawithwith complexescomplexes reaction,rather than 1 withandand the 2 complexes 1 and 2 Whilecanshowingshowingapplication likewise thethe highestbehighestof utilized 4-methyl-1,1 ofcanshowingcan complexamountsamounts likewiselikewise as potentialthe ′ of -biphenylof behighestbe2 isolatedisolated utilizedgenerallyutilized pre-cata amounts product.formedproduct. asas lystspotentialpotential leads of is forHeHeisolated lowered re, tore,the pre-catapre-cata theathe Kumada completeproduct. choice choiceforlystslysts 3 and reaction,ofof forHefor thethe 4 conversion re, ,thethe the counterionscounterions the Kumada Kumada withresults choice complexes clearly ofreaction, reaction, ratherrather the 4-iodotoluene counterionsshow thanthan1 withandwith the thethat 2 complexescomplexes Ni(II) rather to complexes the than 11 andand desired the 22 respectively,showing the to highest theshowingshowing Ni(II) amounts thethecomplex of highesthighest isolated amountsamounts2 product.[23,25]. ofof He isolatedisolatedre, the product.product. choice of HeHe there,re, counterions thethe choicechoice ofofrather thethe counterionscounterions than the ratherrather thanthan thethe showing the highest showing amounts the of highest isolated amounts product. of He isolatedre, the product. choice of He there, counterions the choice ofrather the counterions than the rather0 than the showing the highestcanshowing showinglikewise amounts the thebe of highestutilizedhighest isolated amountsamounts as product. potential ofof He isolatedisolated pre-catare, the product.product. choicelysts offor HeHe the there,re, counterions the theKumada choicechoice ofreaction, ofrather thethe counterionscounterions than with the complexes ratherrather thanthan 1 and thethe 2 coupling An overview productfor of the both observed 1 and 0.5 product mol % catalystyields is loading, provided formation in Table of 3. 4-methyl-1,1Yields given-biphenyl for 4-methyl- was showing the highest amounts of isolated product. Here, the choice of the counterions rather than the observed in solely 72% (1 mol %) and 46% (0.5 mol %), as well as 59% (1 mol %) and 41% (0.5 mol %), 1,1′-biphenyl were determined by GC–MS analysis using 1,1′-biphenyl as an internal calibration 0 standard.yields for complexesIn addition,3 andisolated4, respectively. yields from However, experiments while theapplying amount complex of 4-methyl-1,1 1 are added-biphenyl for comparison.formed is lowered While for application3 and 4, the of results complex clearly 2 showgenerally that Ni(II) leads complexes to a complete can likewise conversion be utilized of as4- iodotoluenepotential pre-catalysts to the desired for the coupling Kumada product reaction, for with both complexes 1 and 0.5 mol1 and %2 catalystshowing loading, the highest formation amounts of 4-methyl-1,1of isolated product.′-biphenyl Here, was the observed choice ofin solely the counterions 72% (1 mol rather %) and than 46% the (0.5 oxidation mol %),state as well of theas 59% nickel (1 molcenter %) seems and 41% to be(0.5 of mol more %), importance. yields for complexes While complexes 3 and 4,revealing respectively. only However, halogenide while ligands the amount like the oftetrahedral 4-methyl-1,1 Ni(I)′-biphenyl complex 1formedor the squareis lowered planar for Ni(II)3 and complex4, the results2 showed clearly high show activity that Ni(II) for the complexes coupling can likewise be utilized as potential pre-catalysts for the Kumada reaction, with complexes 1 and 2 showing the highest amounts of isolated product. Here, the choice of the counterions rather than the

Inorganics 2017, 5, 78 6 of 13 oxidationInorganics 2017 state, 5, 78of the nickel center seems to be of more importance. While complexes revealing6 only of 13 halogenide ligands like the tetrahedral Ni(I) complex 1 or the square planar Ni(II) complex 2 showed high activity for the coupling reaction, the formation of 4-methyl-1,1′-biphenyl by complexes 3 and 4 0 3 4 reaction, the formation of 4-methyl-1,1− -biphenyl− by complexes and comprising non-coordinating comprising− non-coordinating− BF4 or ClO4 counterions is hampered. BF4 or ClO4 counterions is hampered. Table 3. Ni(I)- and Ni(II)-catalyzed Kumada cross-coupling reaction of 4-iodotoluene with Table 3. Ni(I)- and Ni(II)-catalyzed Kumada cross-coupling reaction of 4-iodotoluene with phenylmagnesium bromide. phenylmagnesium bromide.

[Ni] Complex Catalytic Amount of [Ni] Yield (%) [Ni] Complex Catalytic Amount of [Ni] Yield (%) [a] [b] 1 1 11 mol %% 81 81, 100 [a], 100 [b] 1 0.5 mol % 94 [a], 100 [b] 1 0.5 mol % 94 [a], 100 [b] 2 1 mol % 100 [b] [b] 2 2 0.51 mol mol % % 100 [b] 100 2 3 0.51 molmol % % 72 ± 2 100[b] [b] 3 3 0.51 mol mol % % 46 ± 721 [b] ± 2 [b] 3 4 0.51 molmol % % 59 ± 461 [b] ± 1 [b] [b] 4 4 0.51 mol mol % % 41 ± 591 ± 1 [b] [b] [a] Isolated yields.4 [b] Yields determined by GC–MS0.5 mol analysis % using 1,10-biphenyl as an 41 internal ± 1 standard. [a] Isolated yields. [b] Yields determined by GC–MS analysis using 1,1′-biphenyl as an internal standard. The highhigh reactivityreactivity of of both both of theof the Ni(I) Ni(I) and Ni(II)and Ni(II) complexes complexes pointed pointed our attention our attention towards towards possible possibleintermediates intermediates that are formed that are upon formed reaction upon with reaction either phenylmagnesiumwith either phenylmagnesium bromide or 4-iodotoluene. bromide or 4-iodotoluene.Thus, we next performedThus, we next stoichiometric performed reactions stoichiometric of the differentreactions Ni of complexesthe different with Ni one complexes equivalent with of oneeither equivalent reagent in of THF. either Subsequently, reagent in eachTHF. solution Subseq wasuently, analyzed each solution by UV/Vis was spectroscopy analyzed by (Figure UV/Vis1). spectroscopyThe UV/Vis spectrum(Figure 1). of The Ni(I) UV/Vis complex spectrum1 has of a broadNi(I) complex absorption 1 has band a broad at low absorption wavelengths band withat low a wavelengthsmaximum at with 385 nma maximum (Figure1A). at 385 Spectra nm (Figure of 2, 3 1A).and Spectra4 differ of significantly 2, 3 and 4 differ from thesignificantly spectrum from of 1. theWhile spectrum the UV/Vis of 1. spectrumWhile the ofUV/Vis2 has anspectrum absorption of 2 maximumhas an absorption at a wavelength maximum of 465at a nm,wavelength the spectra of 465of 3 nm,and the4, which spectra are of nearly 3 and identical,4, which are show nearly an absorption identical, show maximum an absorption at 425 nm maximum and a broader at 425 band nm andwith a a broader lower intensity band with at 670 a nmlower (Figure intensity1B–D). at For 670 complex nm (Figure1, showing 1B–D). anFor absorption complex band1, showing at 385 nm,an absorptionit is apparent band that at the 385 addition nm, it is of apparent 4-iodotoluene that the did addition not lead of to 4-iodotoluene a change in the did complexes’ not lead to electronica change inspectrum the complexes’ (Figure1 A).electronic This observation spectrum (Figure illustrates 1A). that This the observation oxidativeaddition illustrates of that the arylthe iodideoxidative is additionpresumably of the not aryl the iodide first step is presumably in the coupling not processthe first and step no in formation the coupling of a process Ni(III) intermediateand no formation takes ofplace. a Ni(III) Based onintermediate this observation, takes itpl canace. alsoBased be excludedon this observation, that disproportionation it can also of be the excluded Ni(I) complex that disproportionation1 takes place. Addition of the of Ni(I) phenylmagnesium complex 1 takes bromide place. Addition to 1, similarly of phenylmagnesium and regardless of bromide whether to the 1, similarlyexperiments and were regardless performed of whether in the absencethe experiments or presence were of 4-iodotoluene,performed in the led absence only to minoror presence alterations of 4- iodotoluene,of the absorption led only band to around minor 385alterations nm (Inset of Figurethe ab1sorptionA). Fundamentally band around different 385 nm behavior, (Inset Figure however, 1A). Fundamentallywas observed when different the Ni(II) behavior, complex however,2 was investigated was observed (Figure 1whenB). While theaddition Ni(II) complex of 4-iodotoluene 2 was investigatedalso did not lead(Figure to any 1B). change While of ad thedition UV/Vis of 4-iodotoluene spectrum, addition also ofdid phenylmagnesium not lead to any bromidechange of led the to UV/Visa significant spectrum, change addition in the spectrum; of phenylmagnesium the original bandbrom atide 465 led nm to a was significant lost and change a new bandin the centered spectrum; at the385 original nm appeared. band at 465 nm was lost and a new band centered at 385 nm appeared. Identical trends werewere observedobserved forfor thethe Ni(II) Ni(II) complexes complexes3 3and and4 4(Figure (Figure1C,D). 1C,D).Complexes Complexes3 3and and4 4reveal reveal two two characteristic characteristic absorption absorption bands bands at ataround around 430430 andand 670670 nmnm inin THFTHF thatthat disappear after treatment with with phenylmagnesium phenylmagnesium bromide, bromide, suggestin suggestingg an an overall overall similar similar chemistry as observed as observed for complexesfor complexes 1 and1 and2. It is,2. however, It is, however, notable notable that for that complex for complex 3 an additional3 an additional band centered band centered at 465 nm at can465 be nm observed can be observed that was that not wasobserved not observed for the other for the complexes. other complexes. The origin The of origin this additional of this additional band is hithertoband is hithertounknown. unknown. Altogether Altogether it becomes it becomesobvious that obvious Ni complexes that Ni complexes 1–4 do not1– react4 do notwith react only with the arylonly iodide. the aryl A iodide.brief comparison A brief comparison of the electronic of the features electronic of complex features 1 of and complex complexes1 and 2, complexes3 and 4 after2, treatment3 and 4 after with treatment phenylmagnesium with phenylmagnesium bromide clearly bromide suggests clearly similar suggests electronic similar electronicfeatures. features.Thus, it becomesThus, it becomes clear that clear phenylmagnesium that phenylmagnesium additionally additionally acts as a actsreducing as a reducing agent. agent.

Inorganics 2017, 5, 78 7 of 13 Inorganics 2017, 5, 78 7 of 13

AB 0,8 0,8 complex 1 complex 2 + phenyl Grignard + phenyl Grignard + 4-iodotoluene + 4-iodotoluene 0,6 + phenyl Grignard + 4-iodotoluene 0,6 + phenyl Grignard + 4-iodotoluene

0,8

0,4 0,4 0,6 Abs. Abs. Abs.

0,4 0,2 0,2

0,2 360 380 400 420 440 Wavelength (nm) 0,0 0,0

400 500 600 700 800 400 500 600 700 800 Wavelength (nm) Wavelength (nm) CD 0,8 0,8 complex 3 complex 4 + phenyl Grignard + phenyl Grignard + 4-iodotoluene + 4-iodotoluene 0,6 + phenyl Grignard + 4-iodotoluene 0,6 + phenyl Grignard + 4-iodotoluene

0,4 0,4 Abs. Abs.

0,2 0,2

0,0 0,0

400 500 600 700 800 400 500 600 700 800 Wavelength (nm) Wavelength (nm) Figure 1. UV/Vis spectra of complexes 1 (A), 2 (B), 3 (C) and 4 (D) (blue) and their reaction solutions Figure 1. UV/Vis spectra of complexes 1 (A), 2 (B), 3 (C) and 4 (D) (blue) and their reaction solutions with 1 equiv. phenylmagnesium bromide (green), 1 equiv. 4-iodotoluene (red) and with both substrates with 1 equiv. phenylmagnesium bromide (green), 1 equiv. 4-iodotoluene (red) and with both (orange) in THF. substrates (orange) in THF. In addition to our UV/Vis studies, we crystallized the products of the different solutions. In addition to our UV/Vis studies, we crystallized the products of the different solutions. Notably, crystals were obtained from the reaction of complex 1 with phenylmagnesium bromide as well Notably, crystals were obtained from the reaction of complex 1 with phenylmagnesium bromide as as of complexes 2, 3 and 4 with phenylmagnesium bromide and 4-iodotoluene. For all experiments, well as of complexes 2, 3 and 4 with phenylmagnesium bromide and 4-iodotoluene. For all we obtained a yellow crystalline material suitable for X-ray diffraction. The cell parameters of those experiments, we obtained a yellow crystalline material suitable for X-ray diffraction. The cell crystals closely resembled those of complex 1, suggesting the formation of a complex with an overall parameters of those crystals closely resembled those of complex 1, suggesting the formation of a similar structure (Table S1). In addition, the reaction of 4 with phenylmagnesium bromide and complex with an overall similar structure (Table S1). In addition, the reaction of 4 with 4-iodotoluene afforded a second set of crystalline material with slightly enlarged cell parameters phenylmagnesium bromide and 4-iodotoluene afforded a second set of crystalline material with (Table S1). While the quality of this crystal was not sufficiently good, a structural motif was obtained slightly enlarged cell parameters (Table S1). While the quality of this crystal was not sufficiently good, showing a (Triphos)Ni(I) moiety with a coordinated iodine ligand (Figure S1, Table S2). a structural motif was obtained showing a (Triphos)Ni(I) moiety with a coordinated iodine ligand In order to clarify the formation of a Ni(I) species during C–C bond formation, we further (Figure S1, Table S2). conducted electron paramagnetic resonance (EPR) spectroscopy on the same reaction solutions. In order to clarify the formation of a Ni(I) species during C–C bond formation, we further This technique is ideal to elucidate the presence of paramagnetic oxidation states of the transition conducted electron paramagnetic resonance (EPR) spectroscopy on the same reaction solutions. This metal. As previously reported, we found a very rich, albeit greatly overlapping, hyperfine structure for technique is ideal to elucidate the presence of paramagnetic oxidation states of the . complex 1 in THF (Figure S2) [25]. The overall spectrum did not alter upon addition of 4-iodotoluene. As previously reported, we found a very rich, albeit greatly overlapping, hyperfine structure for Addition of phenylmagnesium bromide to the solution of 1, however, lead to broadening of the EPR complex 1 in THF (Figure S2) [25]. The overall spectrum did not alter upon addition of 4-iodotoluene. signal and the hyperfine pattern slightly changed, while the g-value remained unaltered. The latter Addition of phenylmagnesium bromide to the solution of 1, however, lead to broadening of the EPR observation again confirms our hypothesis that complex 1 neither undergoes upon signal and the hyperfine pattern slightly changed, while the g-value remained unaltered. The latter addition of aryl iodides nor shows any disproportionation to afford Ni(0) and Ni(II) species. observation again confirms our hypothesis that complex 1 neither undergoes oxidative addition upon As was reported before, complexes 2, 3 and 4 are EPR silent (Figure2, Figures S3 and S4) addition of aryl iodides nor shows any disproportionation to afford Ni(0) and Ni(II) species. and no change was observed upon addition of 4-iodotoluene [23,25]. As expected from the As was reported before, complexes 2, 3 and 4 are EPR silent (Figure 2, Figures S3 and S4) and no experiments shown above, freeze-quenched reaction solutions of the Ni(II) complexes 2, 3 or 4 change was observed upon addition of 4-iodotoluene [23,25]. As expected from the experiments with added phenylmagnesium bromide revealed an EPR spectrum with identical g-values as for shown above, freeze-quenched reaction solutions of the Ni(II) complexes 2, 3 or 4 with added phenylmagnesium bromide revealed an EPR spectrum with identical g-values as for complex 1 with

InorganicsInorganics2017 2017, ,5 5,, 78 78 88 ofof 1313

phenylmagnesium bromide but with minor changes to the complex hyperfine pattern. Notably, EPR complexspectra of1 with reaction phenylmagnesium mixtures of the bromide complexes butwith and minorthe Grignard changes reagent to the complex as well hyperfine as 4-iodotoluene pattern. Notably,showed EPRsimilar spectra features of reaction as those mixtures without of the4-io complexesdotoluene. andHowever, the Grignard the signal reagent intensity as well was as 4-iodotoluenesignificantly decreased, showed similar suggestin featuresg the as thoseformation without of 4-iodotoluene.an EPR-silent However,species upon the signaladdition intensity of 4- wasiodotoluene. significantly While decreased, crystallographic suggesting datathe showed formation structurally of an EPR-silentrelated cellspecies parameters, upon EPR addition analysis of 4-iodotoluene.suggests that as While well crystallographic as [(Triphos)Ni dataII] found showed during structurally crystallization, related cellat least parameters, one additional EPR analysis Ni(II) I suggestsspecies might that ashave well been as [(Triphos)Niformed duringI] foundsuch experiments. during crystallization, at least one additional Ni(II) species might have been formed during such experiments.

complex 3 + phenyl Grignard + 4-iodotoluene + phenyl Grignard + 4-iodotoluene Intensity

280 300 320 340 360 Magnetic Field (mT)

Figure 2. Electron paramagnetic resonance (EPR) spectrum of complex 3 before (blue) and after reaction Figure 2. Electron paramagnetic resonance (EPR) spectrum of complex 3 before (blue) and after with 1 equiv. phenyl Grignard (green), 1 equiv. 4-iodotoluene (red) and with both 1 equiv. phenyl Grignardreaction with and 11 equiv.equiv. 4-iodotoluenephenyl Grignard (orange) (green), in THF.1 equiv. Experimental 4-iodotoluene conditions: (red) andT with= 10 K,both frequency 1 equiv. 9.63phenyl GHz, Grignard microwave and power 1 equiv. 2 mW, 4-iodotoluene modulation (orange) amplitude in 0.3THF. mT. Experimental conditions: T = 10 K, frequency 9.63 GHz, microwave power 2 mW, modulation amplitude 0.3 mT. As demonstrated by our experiments, the nickel complexes initially react with phenylmagnesium bromideAs anddemonstrated not with 4-iodotoluene.by our experiments, This finding the suggestsnickel thatcomplexes in the Ni(I)-driveninitially react Kumada with cross-couplingphenylmagnesium of aryl bromide iodides and and not a Grignard with 4-iodotoluene. reagent, the This Grignard finding reagent suggests initially that in acts the as Ni(I)-driven a reducing agentKumada for Ni(II)cross-coupling to afford aof Ni(I) aryl species.iodides Suchand a a Grignard scenario wouldreagent, imply the Grignard that phenyl reagent radicals initially originating acts as froma reducing the Grignard agent for might Ni(II) form. to afford While a Ni(I) we were species. not ableSuch to a detectscenario such would species imply in situ,that phenyl we recognized radicals thatoriginating after 24 from h, solutions the Grignard of the might Ni(II) complexesform. While and we phenylmagnesiumwere not able to detect bromide such alwaysspecies containedin situ, we smallrecognized amounts that of after 1,10 -biphenyl24 h, solutions (~1%) of as the analyzed Ni(II) complexes by GC–MS. and This phenylmagnesium assumption is supported bromide always by the factcontained that in thesmall case amounts of an additional of 1,1′-biphenyl treatment of(~1%) complex as analyzed1 with phenylmagnesium by GC–MS. This bromide, assumption we did is notsupported find any by 1,1 the0-biphenyl. fact that in the case of an additional treatment of complex 1 with phenylmagnesium bromide,Based we on did our not experimental find any 1,1′-biphenyl. results we propose the following mechanism for the catalytic cross-couplingBased on reactionour experimental catalyzed resu by thelts we Ni complexespropose the1 –following4 (Scheme mechanism3): for the catalytic cross- coupling reaction catalyzed by the Ni complexes 1–4 (Scheme 3): (1) Starting from Ni(II) complexes 2–4, a reduction to a Ni(I) species by a as (1) Starting from Ni(II) complexes 2–4, a reduction to a Ni(I) species by a Grignard reagent as reducing agent occurs as initial reaction step. This reduction likewise leads to formation of reducing agent occurs as initial reaction step. This reduction likewise leads to formation of 1,1′- 1,10-biphenyl. biphenyl. (2) The Ni(I) species will then undergo transmetalation with a second phenylmagnesium bromide (2) The Ni(I) species will then undergo transmetalation with a second phenylmagnesium bromide molecule. This proposition stems from the observation that the isolated Ni(I) complex 1 does not molecule. This proposition stems from the observation that the isolated Ni(I) complex 1 does not react with aryl iodides. react with aryl iodides.

Inorganics 2017, 5, 78 9 of 13 Inorganics 2017, 5, 78 9 of 13

(3)(3) TheThe reactive Ni(I)–phenyl intermediate formed upon transmetalation then reacts under anan oxidativeoxidative addition addition with with the aryl halogenide. It It is worth mentioning that the generated Ni(III) speciesspecies may may bear bear the the Triphos Triphos ligand ligand either either in in a aκ2κ-2 or- or κ3κ-coordination3-coordination mode. mode. Occupation Occupation of a of κ2 a- coordinationκ2-coordination mode mode seems seems an attractive an attractive option option to reduce to reduce the steric the steric hindranc hindrancee at the at Ni the center Ni center and toand allow to allow for further for further reaction reaction steps steps to proceed. to proceed. (4)(4) Subsequently,Subsequently, the coupling product is released by reductive elimination and the Ni(I) species, nownow bearing an iodide ligand, is regenerated.

Scheme 3.3.Proposed Proposed mechanism mechanism for theforNi-catalyzed the Ni-catalyzed Kumada Kumada cross-coupling cross-coupling reaction withreaction complexes with 1complexes–4. While 1– possible,4. While possible, DFT calculations DFT calculations suggest suggest the formation the formation of the of Ni theIII NiintermediateIII intermediate shown shown in parenthesesin parentheses not not to to be be a significanta significant part part of of the the reaction reaction cycle. cycle. AdditionalAdditional reactionreaction schemescheme forfor the formationformation ofof oneone 1,11,10′-biphenyl molecule starting with 1 and endingending upup withwith [(Triphos)Ni[(Triphos)NiIII]I] withwith calculated ∆ΔG values forfor eacheach reactionreaction step.step.

Quantum-chemical calculations of the reaction enthalpies were performed in order to gaingain support forfor thethe proposedproposed cycle.cycle. Indeed, the calculationscalculations indicated that transmetalation with the I Grignard reagent to form [Triphos)Ni [Triphos)NiI(phenylate)](phenylate)] is is isothermic isothermic (+1 (+1 kc kcal/mol)al/mol) within within the the accuracy accuracy of ofthe the calculations, calculations, and and subsequent subsequent reaction reaction with withiodobenzene iodobenzene is thermodynamically is thermodynamically favored favored for the forκ2- 2 3 thecoordinationκ -coordination mode mode(Scheme (Scheme 3, lower3, lower left) left)but butendothermic endothermic for forthe theκ3-intermediate.κ -intermediate. As such, As such, κ2- κconformation2-conformation presents presents an an ideal ideal scaffold scaffold for for the the two two phenylates phenylates to to become become co-coordinated co-coordinated to the same metal ionion andand inin spatialspatial vicinity.vicinity. Moreover, Moreover, the the respective respective phenyl phenyl planes planes form form an an angle angle of of 90 90 degrees degrees in suchin such a way a way that that the twothe twoπ-systems π-systems significantly significantly overlap overlap at the at carbenes. the carbenes. The latter The likelylatter islikely of crucial is of importancecrucial importance as an onset as an for onset C–C bondfor C–C formation. bond formation. Release of biphenylRelease of and biphenyl subsequent and re-coordinationsubsequent re- coordination of the phosphine arm is highly exothermic (−60 kcal/mol) and gives rise to the biphenyl final product and [(Triphos)NiII], completely in line with experimental observations.

Inorganics 2017, 5, 78 10 of 13 of the phosphine arm is highly exothermic (−60 kcal/mol) and gives rise to the biphenyl final product and [(Triphos)NiII], completely in line with experimental observations. As such, besides giving theoretical support for the proposed mechanism, the calculations additionally underline the importance of the flexibility of the Triphos ligand as a κ2- or κ3-coordinated ligand: it can easily harbor a low-spin 3d8 Ni(II) halide species as a κ3-ligand, which is compatible with a preferred 4-coordinate square-planar coordination of low-spin Ni(II). Upon oxidation to Ni(III), 3d7, which prefers a five-coordinate square mono-pyramidal coordination, one phosphine easily dissociates in order to stabilize this . Upon reductive elimination of biphenyl, re-coordination occurs.

3. Materials and Methods

General procedures. All reactions were performed under a dry N2 or Ar atmosphere I II using standard Schlenk techniques or in a glovebox. [(Triphos)Ni Cl] (1), [(Triphos)Ni Cl2](2), II II [(Triphos)Ni Cl](BF4) and [(Triphos)Ni Cl](ClO4) were synthesized according to previously reported procedures [23,25]. All other compounds were obtained from commercial vendors and used without further purification. All solvents were dried prior to use according to standard methods. 1H-, 13C{1H}-, 19F- and 31P{1H}-NMR spectra were recorded with a Bruker DPX-200 NMR spectrometer or a Bruker DPX-250 NMR spectrometer at room temperature. Peaks were referenced to residual 1H or 13C signals from the deuterated solvent and are reported in parts per million (ppm). Mass spectra were measured with a Shimadzu QP-2010 instrument. UV/Vis spectra were recorded with a Varian Cary 100 spectrometer at room temperature. EPR spectra were recorded at T = 10 K on a Bruker Elexsys E500 X-band spectrometer equipped with an Oxford CF935 flow cryostat and a ST9102 resonator. The microwave frequency amounted to 9.636 GHz in all experiments. A microwave power of 2 mW was used. The modulation amplitude of 0.3 mT was chosen to optimize the S/N ratio. A few additional experiments were performed at lower modulation amplitude, but did not reveal additional or more resolved hyperfine structure. Quantum Chemistry. All calculations were performed with the ORCA program package [26], geometry optimization and frequency analysis was performed by using the BP86 functional [27] and def2-SVP basis set [28] and zeroth order regular approach (zora) [29,30] in order to take into account scalar relativistic effects at nickel and iodine. General procedure for Kumada coupling reactions. The respective potential catalyst (0.5 mol %) was dissolved in anhydrous THF (6 mL) and the corresponding aryl halide (2.8 mmol) was subsequently added. The solution was stirred for 10 min before the addition of the corresponding Grignard reagent (5.6 mmol). The reaction mixture was stirred for 2.5 h at room temperature. Subsequently, methanol was added to quench the reaction. Silica was added to the solution and the solvent was removed. Purification via column chromatography allowed for isolation of the cross-coupling products P1–P7. 1H, 13C and 19F NMR spectra and GC-MS graphics for characterization of the coupling products are placed in Supplementary Materials.

0 1 1,1 -Biphenyl (P1): H NMR (200 MHz, CDCl3): δ = 7.64–7.59 (m, 4H, HAr), 7.50–7.32 (m, 6H, HAr). 13 + C NMR (50 MHz, CDCl3): δ = 141.4, 128.9, 129.4, 127.3. GC–MS (m/z): Calculated for [C12H10] : 154, found: 154.

0 1 4-Methyl-1,1 -biphenyl (P2): H NMR (200 MHz, CDCl3): δ = 7.62–7.29 (m, 8H, HAr), 7.23 (m, 1H, HAr), 13 2.39 (s, 3H, CH3). C NMR (50 MHz, CDCl3): δ = 141.3, 138.5, 137.2, 129.6, 238.9, 128.8, 127.1, 127.1. + GC–MS (m/z): Calculated for [C13H12] : 168, found: 168. 0 1 4-Methoxy-1,1 -biphenyl (P3): H NMR (200 MHz, CDCl3): δ = 7.59–7.50 (m, 4H, HAr), 7.47–7.39 13 (m, 2H, HAr), 7.35–7.27 (m, 1H, HAr), 7.03–6.95 (m, 2H, HAr), 3.86 (s, 3H, CH3). C NMR (50 MHz, CDCl3): + δ = 159.3, 141.0, 133.9, 128.9, 128.3, 126.9, 126.8, 114.4, 55.5. GC–MS (m/z): Calculated for [C13H12O] : 184, found: 184. Inorganics 2017, 5, 78 11 of 13

1 1,4-Diphenylbenzene (P4): H NMR (200 MHz, CDCl3): δ = 7.69–7.62 (m, 8H, HAr), 7.51–7.32 13 (m, 6H, HAr). C NMR (50 MHz, CDCl3): δ = 140.9, 140.3, 129.0, 127.6, 127.5, 127.2. GC–MS (m/z): + Calculated for [C18H14] : 230, found: 230. 0 1 4-Fluoro-1,1 -biphenyl (P5): H NMR (200 MHz, CDCl3): δ = 7.59–7.52 (m, 4H, HAr), 7.49–7.33 13 (m, 3H, HAr), 7.19–7.08 (m, 2H, HAr). C NMR (50 MHz, CDCl3): δ = 162.6 (d, J = 246.2 Hz), 140.4, 137.5 (d, J = 3.3 Hz), 129.0, 128.8 (d, J = 8.0 Hz), 127.4, 127.2, 115.8 (d, J = 21.4 Hz). 19F NMR + (235 MHz, CDCl3): –115.9. GC–MS (m/z): Calculated for [C12H9F] : 172, found: 172. 0 1 3,5-Dimethyl-1,1 -biphenyl (P6): H NMR (200 MHz, CDCl3): δ = 7.62 (d, 2H, HAr), 7.49–7.35 13 (m, 5H, HAr), 7.03 (s, 1H, HAr), 2.42 (s, 6H, CH3). C NMR (50 MHz, CDCl3): δ = 141.6, 141.4, + 138.3, 129.0, 128.7, 127.3, 127.2, 125.2, 21.5. GC–MS (m/z): Calculated for [C14H14] : 182, found: 182. 1 2-Phenylnaphthalene (P7): H NMR (200 MHz, CDCl3): δ = 8.05 (s, 1H, HAr), 7.95–7.85 (m, 3H, HAr), 13 7.78–7.71 (m, 3H, HAr), 7.55–7.35 (m, 5H, HAr). C NMR (50 MHz, CDCl3): δ = 141.3 138.7, 133.8, 132.8, + 129.0, 128.6, 128.3, 127.8, 127.6, 127.5, 126.4, 126.1, 125.9, 125.7. GC–MS (m/z): Calculated for [C16H12] : 204, found: 204.

4. Conclusions In conclusion, we herein showed that the Ni(I) complex 1 can indeed serve as a catalyst in C–C bond formation in Kumada cross-coupling reactions. Using attractive reaction conditions with short reaction times of 2.5 h at room temperature and very low catalytic loadings of 0.5 mol %, the coupling products were obtained in good to excellent yields. Owing to the relatively low tolerance of the Ni(I) complex 1 towards functional groups, the substrate scope for Kumada coupling reactions is limited to alkyl-, alkoxy- and aryl-substituted substrates. We also observed that Ni(II) complexes 2–4 are suitable to catalyze the coupling of aryl iodides with phenylmagnesium bromide. Investigating the reaction solutions of stoichiometric reactions of the Ni complexes with the coupling reagents by UV/vis measurements showed that reaction with the Grignard reagents leads to the same catalytic Ni(I) species for all complexes. Furthermore, the Ni complexes did not react under oxidative addition with aryl iodides. EPR measurements confirmed the formation of a Ni(I) species by adding Grignard reagent to the Ni(II) complexes. This is in line with the results from crystallization experiments, where for several reactions employing compounds 2, 3 or 4, Ni(I) complex 1 was isolated. Based on our findings, we propose that for Kumada cross-coupling reactions with Ni complexes bearing tripodal phosphine ligand Triphos, a monovalent Ni(I) complex acts as the catalytically active species.

Supplementary Materials: The following are available online at www.mdpi.com/2304-6740/5/4/78/s1. Cif and cif checked files. Details of the calculations. Figure S1: Structure of the asymmetric unit of compound 1, Figure S2: EPR Spectrum of complex 1 (blue) and its reaction solutions with 1 equiv. phenyl Grignard (green), 1 equiv. 4-iodotoluene (red) and with both 1 equiv. phenyl Grignard and 1 equiv. 4-iodotoluene (orange) in THF, Figure S3: EPR Spectrum of complex 2 (blue) and its reaction solutions with 1 equiv. phenyl Grignard (green), 1 equiv. 4-iodotoluene (red) and with both 1 equiv. phenyl Grignard and 1 equiv. 4-iodotoluene (orange) in THF, Figure S4: EPR Spectrum of complex 4 (blue) and its reaction solutions with 1 equiv. phenyl Grignard (green), 1 equiv. 4-iodotoluene (red) and with both 1 equiv. phenyl Grignard and 1 equiv. 4-iodotoluene (orange) in THF, Figure S5: 1H NMR (200 MHz) and 13C NMR (50 MHz) spectra and GC-MS of 1,10-biphenyl (P1), Figure S6: 1H NMR (200 MHz) and 13C NMR (50 MHz) spectra and GC-MS of 4-methyl-1,10-biphenyl (P2), Figure S7: 1H NMR (200 MHz) and 13C NMR (50 MHz) spectra and GC-MS of 4-methoxy-1,10-biphenyl (P3), Figure S8: 1H NMR (200 MHz), 13C NMR (50 MHz) and 19F NMR (235 MHz) spectra and GC-MS of 4-fluoro-1,10-biphenyl (P4), Figure S9: 1H NMR (200 MHz) and 13C NMR (50 MHz) and GC-MS of 3,5-dimethyl-1,10-biphenyl (P5), Figure S10: 1H NMR (200 MHz) and 13C NMR (50 MHz) and GC-MS of 1,4-biphenylbenzene (P6), Figure S11: 1H NMR (200 MHz) and 13C NMR (50 MHz) and GC-MS of 2-phenylnaphthalene (P7), Table S1: Cell Parameters of complex 1 and of crystals obtained from the stoichiometric reactions solutions of 1 with 1 equiv. phenylmagnesium bromide, and of 2, 3 or 4 with both 1 equiv. phenylmagnesium bromide and 1, Table S2: Crystal data and structure refinement of [(Triphos)NiII], Data S1: Cartesian coordinates [Angstrom] of geometry-optimized models used in the calculations. Acknowledgments: This work was supported by the Fonds der Chemischen Industrie (Liebig grant to Ulf-Peter Apfel) and through the Deutsche Forschungsgemeinschaft (Emmy Noether grant to Ulf-Peter Apfel, AP242/2-1). Inorganics 2017, 5, 78 12 of 13

Author Contributions: Linda Iffland, Anette Petuker and Ulf-Peter Apfel conceived and designed the experiments; Linda Iffland and Anette Petuker performed the experiments. All authors were involved in the analysis of the data; Maurice van Gastel performed DFT calculations and EPR spectroscopy. All authors were involved in writing the paper. Conflicts of Interest: The authors declare no conflict of interest.

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