With Axial Chirality Via Double Cyclometalation of 2,20-Bis(Aminomethyl)-1,10-Binaphthyl

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Article New Bifunctional Bis(azairidacycle) with Axial Chirality via Double Cyclometalation of 2,20-Bis(aminomethyl)-1,10-binaphthyl

Yasuhiro Sato 1,2, Yuichi Kawata 1, Shungo Yasui 1, Yoshihito Kayaki 1,* and Takao Ikariya 1,†

1 Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1-E4-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan; [email protected] (Y.S.); [email protected] (Y.K.); [email protected] (S.Y.) 2 Hazardous Materials Laboratory, Research and Development Division, National Research Institute of Fire and Disaster, Jindaiji-higashimachi 4-35-3, Chofu, Tokyo 182-8508, Japan * Correspondence: [email protected]; Tel.: +81-3-5734-2881 † Deceased on 21 April 2017.

Abstract: As a candidate for bifunctional asymmetric catalysts containing a half-sandwich C–N chelating Ir(III) framework (azairidacycle), a dinuclear Ir complex with an axially chiral linkage is newly designed. An expedient synthesis of chiral 2,20-bis(aminomethyl)-1,10-binaphthyl (1) from 1,1-bi-2-naphthol (BINOL) was accomplished by a three-step process involving nickel-catalyzed

cyanation and subsequent reduction with Raney-Ni and KBH4. The reaction of (S)-1 with an equimo- 5 lar amount of [IrCl2Cp*]2 (Cp* = η –C5(CH3)5) in the presence of sodium acetate in acetonitrile at 80 ◦C gave a diastereomeric mixture of new dinuclear dichloridodiiridium complexes (5) through the double C–H bond cleavage, as conﬁrmed by 1H NMR spectroscopy. A loss of the central chirality

on the Ir centers of 5 was demonstrated by treatment with KOC(CH3)3 to generate the corresponding 16e amidoiridium complex 6. The following hydrogen transfer from 2-propanol to 6 provided di-

Citation: Sato, Y.; Kawata, Y.; Yasui, S.; astereomers of hydrido(amine)iridium retaining the bis(azairidacycle) architecture. The dinuclear Kayaki, Y.; Ikariya, T. New Bifunctional chlorido(amine)iridium 5 can serve as a catalyst precursor for the asymmetric transfer hydrogenation Bis(azairidacycle) with Axial Chirality of acetophenone with a substrate to a catalyst ratio of 200 in the presence of KOC(CH3)3 in 2-propanol, via Double Cyclometalation of 2,20- leading to (S)-1-phenylethanol with up to an enantiomeric excess (ee) of 67%. Bis(aminomethyl)-1,10-binaphthyl. Molecules 2021, 26, 1165. https://doi. Keywords: bifunctional catalyst; metal-ligand cooperation; dinuclear complex; iridacycle; cyclometa- org/10.3390/molecules26041165 lation; asymmetric transfer hydrogenation; cyanation; 1,1-binaphthyl; axial chirality

Academic Editor: Vincent Ritleng

Received: 31 January 2021 1. Introduction Accepted: 18 February 2021 Published: 22 February 2021 The metal/NH bifunctional catalysis has become a pivotal concept for redox transformations based on hydrogen transfer between secondary alcohols and ketones [1–5]. From in-depth studies on original (η6-arene)Ru catalysts bearing chiral N-sulfonyldiamines Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in (N–N chelate complexes) developed by Noyori and Ikariya [6,7], a fundamental hydrogen published maps and institutional affil- delivery process associated with alternating back and forth between 16e amido and 18e iations. hydrido(amine) complexes has been thoroughly realized. We have systematically investigated how the interconversion operates in a range of group 8 and 9 metal complexes with protic amine chelates, and we also investigated how ligand modification, by changing the chelating atom, significantly influences the catalyst performance [2,8,9]. In particular, half-sandwich (η6-arene)Ru, Cp*Ir, and Cp*Rh complexes containing a five-membered Copyright: © 2021 by the authors. bifunctional C–N chelate ring, which were synthesized by the orthometalation of protic Licensee MDPI, Basel, Switzerland. This article is an open access article benzylamine derivatives [10–13], have been applied to efficient bifunctional catalysts based distributed under the terms and on the amine/amido functionalities (Scheme1)[ 14–26]. Compared to the prototype N–N conditions of the Creative Commons chelate Ir complex, remarkable enhancement in the transfer hydrogenation of ketones in Attribution (CC BY) license (https:// 2-propanol [12] and in the aerobic oxidation of alcohols were observed [13]. The rapid creativecommons.org/licenses/by/ hydrogen transfer from alcohols to the amidoiridium and from the hydrido(amine)iridium 4.0/). to ketones also accommodates the dynamic kinetic resolution of racemic secondary alcohols

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Molecules 2021, 26, 1165 2 of 12 of ketones in 2-propanol [12] and in the aerobic oxidation of alcohols were observed [13]. The rapid hydrogen transfer from alcohols to the amidoiridium and from the hydrido(amine)iridium to ketones also accommodates the dynamic kinetic resolution of ra- cemicby combination secondary with alcohols enzymatic by combination transesteriﬁcation with enzymatic using Candida transesterification antarctica lipase using B Can- [21]. Thedida uniqueantarctica catalytic lipase functionB [21]. The could unique be enhanced catalytic byfunc thetion high could basicity be enhanced of the amido by the moiety high basicityas well asof strongthe amido nucleophilicity moiety as well of theas strong hydrido nucleophilicity ligand with theof the aid hydrido of the pronounced ligand with theσ-donor aid of nature the pronounced of the coordinating σ-donor nature carbon of atom. the coordinating carbon atom.

Scheme 1. Transfer hydrogenationhydrogenation between between alcohols alcohols and an ketonesd ketones based based on the on metal/NH the metal/NH bifunctionality bifunc- . tionality. The asymmetric versions of amidoiridium have been synthesized by the orthometa- lationThe of 1-phenyl-1-aminoalkanesasymmetric versions of withamidoiridium a chiral center have at thebeen benzylic synthesized position by and the have or- providedthometalation reasonable of 1-phenyl-1-aminoalkanes enantioselectivities in thewith asymmetric a chiral center transfer at hydrogenationthe benzylic position of ace- andtophenone have provided [25]. The reasonable structural enantioselectivi studies on theties isolable in the catalytic asymmetric intermediates transfer hydrogena- suggested tionthat theof acetophenone effective asymmetric [25]. The induction structural is intimately studies on bound the isolable up with catalytic decent diastereomeric intermediates suggestedcontrol in thethat formation the effective of hydrido(amine)iridium asymmetric induction possessingis intimately central bound chirality up with at decent the metal di- astereomericby a one-sided control approach in the of formation the hydrogen of hydrido(amine)iridium donor, 2-propanol, to possessing amidoiridium. central Related chiral- itycationic at the Ru, metal Rh, by and a one-sided Ir complexes approach bearing of cyclometalatedthe hydrogen donor, C–N 2-propanol, chelates were to intensivelyamidoirid- ium.investigated Related bycationic Pfeffer Ru, and Rh, coworkers and Ir complexes [14–20] bearing from screening cyclometalated experiments C–N chelates using a were vari- intensivelyety of chiral investigated benzylic amine by Pfeffer ligands, and but cowo catalyticallyrkers [14–20] active from amido screening and hydrido(amine)experiments us- ingcomplexes a variety have of notchiral been benzylic characterized. amine ligands, but catalytically active amido and hydrido(amine)Separately, complexes it has been have reported not been that characterized. dinuclear complexes, in which the mononuclear structureSeparately, is extended it has bybeen bridging reported ligands, that dinu exhibitclear characteristic complexes, in properties which the and mononuclear favorable structurecatalytic performance is extended by compared bridging to ligands, the parent exhibit mononuclear characteristic complexes properties [27– 34and]. Thanksfavorable to catalyticthe cooperative performance effect, incompared which the to reaction the parent sites mononuclear on multiple metals complexes play different[27–34]. Thanks roles, and to the uniquecooperative electronic effect, structure in which of the the reaction conjugated sites bridging on multiple ligands, metals the catalyticplay different activity roles, and andenantioselectivity the unique electronic can be improvedstructure of by the multinuclear conjugated assembly.bridging ligands, In particular, the catalytic as beneﬁcial activ- ityapplications and enantioselectivity of optically active can be dinuclear improved transition by multinuclear metal complexes assembly. with In axialparticular, chirality as beneficialintroduced applications into the bridging of optically moiety, active Toste dinuclear et al. have transition demonstrated metal complexes the gold-catalyzed with axial chiralitydynamic introduced kinetic resolution into the of bridging propargylic moiety, esters Toste [32] andet al. Sasai have et demonstrated al. have demonstrated the gold- catalyzedthe vanadium-catalyzed dynamic kinetic asymmetric resolution oxidative of prop couplingargylic esters of aromatic [32] and compounds Sasai et [al.33 ,34have]. demonstratedEncouraged the by vanadium-catalyzed these works, we focused asymme ourtric interest oxidative on a dimetallic coupling compoundof aromatic with com- a poundschiral diamido [33,34]. linkage formed by the double orthometalation of benzylic diamine shown in SchemeEncouraged2. It is by expected these works, that inherentwe focused intramolecular our interest on steric a dimetallic effects arising compound from with the adiscrete chiral symmetricaldiamido linkage bis(metallacycle) formed by willthe contributedouble orthometalation to enhance the catalyticof benzylic performance diamine compared with the mononuclear C–N chelate complexes. We report here a synthetic shown in Scheme 2. It is expected that0 inherent intramolecular0 steric effects arising from theapproach discrete toward symmetrical optically bis(metallacycle) active 2,2 -bis(aminomethyl)-1,1 will contribute to-binaphthyl enhance the (1) catalytic and its transfor- perfor- mancemation compared into a new with chiral the dinuclear mononuclear azairidacycle. C–N chelate Furthermore, complexes. catalytic We report application here a to syn- the theticasymmetric approach transfer toward hydrogenation optically active of acetophenone 2,2′-bis(aminomethyl)-1,1 using 2-propanol′-binaphthyl was also (1 explored.) and its transformation into a new chiral dinuclear azairidacycle. Furthermore, catalytic application to the asymmetric transfer hydrogenation of acetophenone using 2-propanol was also explored.

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H H H N H N Ir H2N Ir H2N Ir Ir NH2 N NH2 N H H H H 1 1 Scheme 2. Retrosynthesis of bis(azairidacycle) with an axially chiral binaphthyl linkage. SchemeScheme 2.2. RetrosynthesisRetrosynthesis ofof bis(azairidacycle)bis(azairidacycle) withwith anan axiallyaxially chiralchiral binaphthylbinaphthyllinkage. linkage. 2. Results and Discussion 2.2. ResultsResults andand DiscussionDiscussion 2.1. A Short-Cut Synthesis of 2,2′0-Bis(aminomethyl)-1,10′-Binaphthyl 2.1.2.1. AA Short-CutShort-Cut SynthesisSynthesis ofof 2,22,2′-Bis(aminomethyl)-1,1-Bis(aminomethyl)-1,1′-Binaphthyl-Binaphthyl The axially chiral diamine 1 has been synthesized by the reductive transformation of TheThe axiallyaxially chiral chiral diamine diamine1 1has has been been synthesized synthesized by by the the reductive reductive transformation transformation of di- of diazo or dicarboxamide compounds as reported independently by Shi [35] and Tomioka azodiazo or or dicarboxamide dicarboxamide compounds compounds as reportedas report independentlyed independently by Shi by [Shi35] and[35] Tomiokaand Tomioka [36] [36] (for each route A and B in Scheme 3); however, these precursors are obtained via (for[36] each(for routeeach route A and A B and in Scheme B in Scheme3); however, 3); however, these precursors these precursors are obtained are obtained via multi- via multistep procedures starting with BINOL. As a simple synthetic strategy enabling C–C stepmultistep procedures procedures starting starting with BINOL.with BINOL. As a simple As a simple synthetic synthetic strategy strategy enabling enabling C–C bond C–C bond construction on the0 1,1′-binaphthyl scaffold and amine functionalization, we exam- constructionbond construction on the on 1,1 the-binaphthyl 1,1′-binaphthyl scaffold scaffold and amine and amine functionalization, functionalization, we examined we exam- a ined a three-step sequence involving the catalytic dicyanation of easily accessible BINOL three-stepined a three-step sequence sequence involving involving the catalytic the cata dicyanationlytic dicyanation of easily accessibleof easily accessible BINOL ditriﬂate BINOL ditriflate (2; > 99% enantiomeric excess (ee)) and the following reduction of the C–N triple (ditriflate2; >99% enantiomeric(2; > 99% enantiomeric excess (ee)) excess and the(ee)) following and the following reduction reduction of the C–N of triple the C–N bonds triple to bonds to the aminomethyl group (route C). thebonds aminomethyl to the aminomethyl group (route group C). (route C).

HO Br N HO Br N3 OH 3 OH Br N3 Br N3 2 steps 2 steps

route A 3 steps H2NC(O) route A 3 steps H2NC(O) TfO TfO OTf CONH2 OTf CONH2 route B route B

2 2 H N NC H2 N NC 2 CN CN route C NH2 route C NH2

3 1 3 1 . . Scheme 3. Synthetic routes to 2,20′-bis(aminomethyl)-1,1′0-binaphthyl,-binaphthyl, 1.. Scheme 3. Synthetic routes to 2,2′-bis(aminomethyl)-1,1′-binaphthyl, 1. The cyanationcyanation ofof aryl aryl halides halides and and pseudo-halides pseudo-halides with with cyanide cyanide salts salts has beenhas disclosedbeen dis- The cyanation of aryl halides and pseudo-halides with cyanide salts has been dis- closedby using by Niusing or Pd Ni catalystsor Pd catalysts [37–43 ].[37–43]. To overcome To overcome catalyst catalyst deactivation deactivation by cyanide by cyanide anion closed by using Ni or Pd catalysts [37–43]. To overcome catalyst deactivation by cyanide aniondue to due its strong to its strong coordination coordination ability, ability, some Cu some and Cu Zn cocatalystsand Zn cocatalysts have been have reported been re- to anion due to its strong coordination ability, some Cu and Zn cocatalysts have been re- portedbe effective to be [effective44,45]. Nevertheless, [44,45]. Nevertheless, the employment the employment of 2 as the of 2 substrate as the substrate for dicyanation for dicy- ported to be effective [44,45]. Nevertheless, the employment of 2 as the substrate for dicy- anationshown inshown Scheme in 3Scheme remains 3 remains far less explored,far less explored, and there and is stillthere room is still for room improvement for improve- in anation shown in Scheme 3 remains far less explored, and there is still room for improve- mentterms in of terms practicality of practicality [46,47]. [46,47]. Although Although it was reported it was reported that a limited that a limited amount amount (10%) of(10%) the ment in terms of practicality [46,47]. Although it was reported that a limited amount (10%)

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dinitrileof the dinitrile product product (3) was ( obtained3) was obtained in a Ni/PPh in a Ni/PPh/Zn three-component3/Zn three-component catalyst, catalyst, we found we of the dinitrile product (3) was obtained in a 3Ni/PPh3/Zn three-component catalyst, we found that switching the phosphorus ligand to chelate phosphines resulted in the prefer- thatfound switching that switching the phosphorus the phosphorus ligand ligand to chelate to chelate phosphines phosphines resulted resulted in the in preferential the preferential formation of the dinitrile rather than the mononitrile (4) (Scheme 4). Some typical formationential formation of the dinitrileof the dinitrile rather thanrather the than mononitrile the mononitrile (4) (Scheme (4) (Scheme4). Some 4). typical Some results typical results are summarized in Table 1. When the reaction of (S)-2 with KCN (1.1 equiv) was areresults summarized are summarized in Table1 in. When Table the1. When reaction the of reaction ( S)-2 with of KCN(S)-2 with (1.1 equiv) KCN was(1.1 equiv) performed was usingperformed NiCl 2using(dppe) NiCl (102(dppe) mol%) (10 with mol%) an extra with amountan extra amount (10 mol%) (10 ofmol%) DPPE of (DPPEDPPE (DPPE = 1,2- performed using NiCl2(dppe) (10 mol%) with an extra amount (10 mol%) of DPPE (DPPE bis(diphenylphosphino)ethane)= 1,2-bis(diphenylphosphino)ethane) in the in presence the presence of Zn of powder Zn powder (30 mol(30 mol %) under%) under reﬂux re- = 1,2-bis(diphenylphosphino)ethane) in the presence of Zn powder (30 mol %) under re- conditionsflux conditions for 24 for h, 24 a h, high a high boiling boiling point point solvent, solvent, DMF DMF (N (N,N,N-dimethylformamide),-dimethylformamide), waswas flux conditions for 24 h, a high boiling point solvent, DMF (N,N-dimethylformamide), was foundfound to be be superior superior to to 1,4-dioxane 1,4-dioxane and and acetonitrile acetonitrile (entries (entries 1–3). 1–3). To our To delight, our delight, (S)-3 was (S)- found to be superior to 1,4-dioxane and acetonitrile (entries 1–3). To our delight, (S)-3 was 3obtainedwas obtained in 87% inyield 87% without yield without loss of the loss opti ofcal the purity optical (>99% purity ee). (>99% The use ee). of The additional use of obtained in 87% yield without loss of the optical purity (>99% ee). The use of additional additionalphosphine phosphinewas advantageous was advantageous for the cyanation, for the cyanation, possibly preventing possibly preventing excessive excessivecoordina- phosphine was advantageous for the cyanation, possibly preventing excessive coordina- coordinationtion of the cyanide of the cyanideanion. Other anion. chelate Other phosphines chelate phosphines (entries (entries4 and 5) 4 and and the 5)and Pd variant the Pd tion of the cyanide anion. Other chelate phosphines (entries 4 and 5) and the Pd variant variant(entry 6) (entry resulted 6) resulted in a decrease in a decrease in the in theyield yield of of3. 3The. The subsequent subsequent reduction reduction of of 3 waswas (entry 6) resulted in a decrease in the yield of 3. The subsequent reduction of 3 was achievedachieved byby aa combinedcombined useuse ofof Raney-NiRaney-Ni andand KBHKBH44 [[48],48], whereaswhereas itit hashas beenbeen reportedreported thatthat achieved by a combined use of Raney-Ni and KBH4 [48], whereas it has been reported that onlyonly tracetrace amountsamounts ofof thethe desireddesired diamine were produced in some other approaches [[47].47]. only trace amounts of the desired diamine were produced in some other approaches [47]. AfterAfter optimizationoptimization ofof thethe reactionreaction conditions,conditions, treatmenttreatment withwith excessexcess Raney-NiRaney-Ni (4(4 equiv)equiv) After optimization of the reaction conditions,◦ treatment with excess Raney-Ni (4 equiv) andand KBHKBH44 (8(8 equiv)equiv) inin ethanolethanol at at 50 50 C°C for for 3 3 h h gave gave (S ()-S1)-1in in a gooda good yield yield of of 83% 83% (Scheme (Scheme5; and KBH4 (8 equiv) in ethanol at 50 °C for 3 h gave (S)-1 in a good yield of 83% (Scheme Figures5; Figures S4 S4 and and S5, S5, In theIn the Supplementary Supplementary Materials). Material). 5; Figures S4 and S5, In the Supplementary Material).

Scheme 4. Catalytic cyanation of ditriﬂate 2. Scheme 4. Catalytic cyanation of ditriflate 2. Scheme 4. Catalytic cyanation of ditriflate 2. Table 1. Catalytic cyanation of 2. Table 1. Catalytic cyanation of 2. Table 1. Catalytic cyanation of 2. 1 %% YieldYield 1 EntryEntry CatCat LigandLigand SolventSolvent % Yield 1 Entry Cat Ligand Solvent 33 44 3 4 1 NiCl2(dppe) DPPE Dioxane 2 n.d.2 2 1 NiCl (dppe) DPPE Dioxane 2 n.d. 2 1 NiCl22(dppe) DPPE Dioxane 2 n.d. 22 NiClNiCl22(dppe)(dppe) DPPEDPPE CH CH33CNCN 1919 17 17 2 NiCl2(dppe) DPPE CH3CN 19 17 33 NiClNiCl22(dppe)(dppe) DPPEDPPE DMF DMF 87 87 0 0 3 NiCl2(dppe) DPPE DMF 87 0 44 NiClNiCl22(dppp)(dppp) DPPPDPPP DMF DMF 57 57 5 5 4 NiCl2(dppp) DPPP DMF 57 5 2 55 NiClNiCl22(dppf)(dppf) DPPFDPPF DMF DMF 17 17 n.d. n.d. 2 5 NiCl2(dppf) DPPF DMF 17 n.d.2 2 66 PdClPdCl22(dppe)(dppe) DPPEDPPE DMF DMF 59 59 n.d. n.d. 2 6 PdCl2(dppe) DPPE DMF 59 n.d. 2 11 IsolatedIsolated yield. yield.2 Not2 Not determined. determined. 1 Isolated yield. 2 Not determined.

H2N NC Raney-Ni 4 equiv H N NC NC 2 NC CN + KBH4 Raney-Ni 4 equiv + + KBH4 EtOH + CN 8 equiv EtOH NH2 NH2 8 equiv 50 °C, 3 h NH2 NH2 50 °C, 3 h

3 83% yield <1% yield 3 83% yield <1% yield Scheme 5. Reduction of 3 with Raney-Ni and KBH4. SchemeScheme 5.5. ReductionReduction ofof 33 withwith Raney-NiRaney-Ni andand KBHKBH44.. 2.2.2.2. Synthesis ofof Bis(azairidacycle)Bis(azairidacycle) viavia DoubleDouble CyclometalationCyclometalation 2.2. Synthesis of Bis(azairidacycle) via Double Cyclometalation AccordingAccording toto our our original original synthetic synthetic procedure procedure for azairidacycles for azairidacycles [12], the [12], orthometala- the or- According to our original synthetic procedure for azairidacycles [12], the or- tionthometalation of enantiopure of enantiopure2 was performed 2 was performed by mixing [Cp*IrClby mixing2]2 [Cp*IrClwith a 2.22]2 molarwith a amount 2.2 molar of thometalation of enantiopure 2 was performed by mixing [Cp*IrCl2]2 with a 2.2 molar sodiumamount acetateof sodium (1.1 acetate equiv/Ir) (1.1 in equiv/Ir) acetonitrile in acetonitrile at 80 ◦C for at 1580 h.°C After for 15 the h. After removal the ofremoval acetic amount of sodium acetate (1.1 equiv/Ir) in acetonitrile at 80 °C for 15 h. After the removal acidof acetic and acid the remaining and the remaining salts from salts the from reaction the mixturereaction throughmixture thethrough work-up the work-up process, newpro- of acetic acid and the remaining salts from the reaction mixture through the work-up pro- dichloridodiiridium (5) having an axially chiral 1,10-binaphthyl linkage was obtained as a

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cess, new dichloridodiiridium (5)) havinghaving anan axiallyaxially chiralchiral 1,11,1′′-binaphthyl-binaphthyl linkagelinkage waswas ob-ob- yellowtainedtained asas powder aa yellowyellow in 69% powderpowder yield inin (Scheme 69%69% yieldyield6). (Schem Based(Schem one 6). the Based electrospray on the electrospray ionization mass ionization spec- trummass (ESI-MS)spectrum displaying (ESI-MS) displaying characteristic characteristic ion peaks at ionm/ zpeaks999.3 at and m// 1001.3z 999.3999.3for andand a fragment1001.31001.3 forfor of aa 1 Cfragmentfragment42H48N2 ofofClIr CC42242,H a4848 completionN22ClIr22,, aa completioncompletion of the double ofof thethe cyclometalation doubledouble cyclometalationcyclometalation was conﬁrmed. waswas confirmed.confirmed. The H NMR TheThe 1 spectrum1H NMR spectrum of 5 in CD of2Cl 52 ininexhibited CDCD22Cl22 exhibitedexhibited a singlet signal aa singletsinglet at 1.73 signalsignal ppm atat due 1.731.73 to ppmppm the methylduedue toto thethe protons methylmethyl of theprotons Cp* ligandof the Cp* along ligand with along two minor with two singlet minor signals singlet at 1.69 signals and at 1.71 1.69 ppm, and which 1.71 ppm, suggested which thesuggested formation the offormation a diastereomeric of a diastereomeric mixture caused mixture by thecaused chirality by the at iridiumchirality (Figureat iridium S6, In(Figure(Figure the Supplementary S6,S6, InIn thethe SupplementarySupplementary Materials). Material).Material).

SchemeScheme 6.6. SynthesisSynthesis ofof dichloridodiiridiumdichloridodiiridium 55 viavia doubledouble orthometalation.orthometalation.orthometalation.

InIn fact,fact, the the subsequentsubsequent treatmenttreatment treatment ofof of 55 withwithwith 22 2 equivalentsequivalents equivalents ofof of KOC(CHKOC(CH KOC(CH33))333 in)in3 inCDCD CD22Cl222 Cl ledled2 ledtoto thethe to thegenerationgeneration generation ofof aa ofcoordinativelycoordinatively a coordinatively unsaturatedunsaturated unsaturated amidoiridiumamidoiridium amidoiridium speciesspecies species ((6)) withwith (6) withaa colorcolor a colorchange change from fromorange orange to dark to darkred purple red purple (Scheme (Scheme 7), thereby7), thereby simplifying simplifying the spectrum the spectrum ow- owinginging toto aa to lossloss a loss ofof thethe of thecentralcentral central chiralitychirality chirality atat thethe at iridiumiridium the iridium atoms.atoms. atoms. AsAs shownshown As shown inin FigureFigure in Figure 1,1, thethe1 signalsignal, the signalattributed attributed to the tomethyl the methyl group group of Cp* of ligand Cp* ligand converged converged to a tosimple a simple peak peak at 1.98 at 1.98 ppm. ppm. In Inanalogy analogy with with the the mononuclear mononuclear C–N C–N chelate chelate complexes, complexes, a a marked marked downfield downﬁeld shift trendtrend 1 1 relativerelative toto the NH 22 signalssignalssignals ofof of amineamine amine complexescomplexes complexes waswas was observedobserved observed inin in thethe the 1HH NMR NMR spectrum spectrum of of6 exhibitingexhibiting6 exhibiting thethe the amidoamido amido signalsignal signal atat at 8.208.20 8.20 ppm.ppm. ppm. ThTh Theseese spectroscopic spectroscopic results corroboratecorroborate thatthat reactantreactant 55 waswaswas comprisedcomprisedcomprised ofofof thethethe stereoisomersstereoisomstereoisomers ofof chlorido(amine)iridium.chlorido(amine)iridium.

H H H N Cl KOC(CH ) N KOC(CH3)3 IrIr 2 equiv IrIr CD Cl IrIr CD2Cl2 IrIr Cl N N H H H 5 6 5 6 SchemeScheme 7.7. FormationFormation ofof coordinativelycoordinatively unsaturatedunsaturated amidoiridium amidoiridium complex complex by by dehydrochlorination dehydrochlorina- oftiontion5. ofof 5.. The 16-electron amidoiridium complex 6 was convertible into the corresponding hydrido(amine)iridium quantitatively in 2-propanol at room temperature for 2 h (Scheme8), in a similar fashion to the mononuclear complexes [12,25]. After removal of the solvent from the reaction mixture under reduced pressure, the resulting white solid was dissolved 1 in CD2Cl2, and the H NMR spectrum was recorded. As shown in Figure2, four signals in the hydride region at –12.81, –12.86, −12.88, and –12.90 ppm are attributable to formation of three diastereomers involving two homochiral (RIrRIr and SIrSIr forms) and one here- rochiral (an RIrSIr form) diiridium centers (Scheme8). Given the fact that the two signals with identical intensity at –12.86 and –12.88 ppm can be assigned to the latter diastereomer having inequivalent C–N chelating hydridoiridium fragments, the stereoisomers were formed in a ratio of 2:4:5. The 1H NMR spectrum also showed singlet signals with the similar intensity ratio at around 1.9 ppm due to the methyl protons of Cp* ligand coordinated to the C2-symmetric bis(azairidacycle)s and the unsymmetrical stereoisomer. The relative ratios were not altered by lowering the measurement temperature.

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Figure 1. Selected 1H NMR spectrum of 6 in CD2Cl2.

The 16-electron amidoiridium complex 6 was convertible into the corresponding hydrido(amine)iridium quantitatively in 2-propanol at room temperature for 2 h (Scheme 8), in a similar fashion to the mononuclear complexes [12,25]. After removal of the solvent from the reaction mixture under reduced pressure, the resulting white solid was dissolved in CD2Cl2, and the 1H NMR spectrum was recorded. As shown in Figure 2, four signals in the hydride region at –12.81, –12.86, −12.88, and –12.90 ppm are attributable to formation of three diastereomers involving two homochiral (RIrRIr and SIrSIr forms) and one herero- chiral (an RIrSIr form) diiridium centers (Scheme 8). Given the fact that the two signals with identical intensity at –12.86 and –12.88 ppm can be assigned to the latter diastereomer having inequivalent C–N chelating hydridoiridium fragments, the stereoisomers were formed in a ratio of 2:4:5. The 1H NMR spectrum also showed singlet signals with the similar intensity ratio at around 1.9 ppm due to the methyl protons of Cp* ligand coordinated to the C2-symmetric1 bis(azairidacycle)s and the unsymmetrical stereoisomer. The FigureFigure 1. 1.SelectedSelected 1H HNMR NMR spectrum spectrum of of6 in6 inCD CD2Cl22Cl. 2. relative ratios were not altered by lowering the measurement temperature. The 16-electron amidoiridium complex 6 was convertible into the corresponding hydrido(amine)iridium quantitatively in 2-propanol at room temperature for 2 h (Scheme 8), in a similar fashion to the mononuclear complexes [12,25]. After removal of the solvent from the reaction mixture under reduced pressure, the resulting white solid was dissolved in CD2Cl2, and the 1H NMR spectrum was recorded. As shown in Figure 2, four signals in the hydride region at –12.81, –12.86, −12.88, and –12.90 ppm are attributable to formation of three diastereomers involving two homochiral (RIrRIr and SIrSIr forms) and one herero- chiral (an RIrSIr form) diiridium centers (Scheme 8). Given the fact that the two signals with identical intensity at –12.86 and –12.88 ppm can be assigned to the latter diastereomer having inequivalent C–N chelating hydridoiridium fragments, the stereoisomers were formed in a ratio of 2:4:5. The 1H NMR spectrum also showed singlet signals with the Molecules 2021, 26, 1165 similar intensity ratio at around 1.9 ppm due to the methyl protons of Cp* ligand coordi-7 of 12

nated to the C2-symmetric bis(azairidacycle)s and the unsymmetrical stereoisomer. The relative ratios were not altered by lowering the measurement temperature. SchemeScheme 8.8. TransformationTransformation of of6 6into into hydrido(amine)iridium hydrido(amine)iridium complexes. complexes.

Scheme 8. Transformation of 6 into hydrido(amine)iridium complexes. FigureFigure 2. 2. SelectedSelected 1H1H NMR NMR spectrum spectrum of of a astreoisomeric streoisomeric mixture mixture of of hydridoiridium hydridoiridium generated from 6 6 withwith 2-propanol.2-propanol.

2.3.2.3. Catalytic Catalytic Application Application to to the the Asymmetric Asymmetric Transfer Transfer Hydrogenation Hydrogenation of of Acetophenone Acetophenone in in2-Propanol 2-Propanol BasedBased on on the the smooth smooth formation formation of of amidoiridium amidoiridium and and hydrido(amine)iridium hydrido(amine)iridium in in the the bis(azairidacycle)bis(azairidacycle) system, system, we we further further explored explored its itscatalytic catalytic potential potential for forthe the asymmetric asymmet- transferric transfer hydrogenation. hydrogenation. The reaction The reaction of acet ofophenone acetophenone in 2-propanol in 2-propanol containing containing the cata- the lystcatalyst precursor precursor 5 with5 witha substrate/iridium a substrate/iridium ratio ratioof 200 of at 200 30 at °C 30 proceeded◦C proceeded to give to give (S)-1- (S)- phenylethanol1-phenylethanol in 60% in 60% yield yield with with a moderate a moderate ee eeof of60% 60% after after 1 1h h(Scheme (Scheme 9).9). When When the the reduction was carried out at −30 °C for 12 h, a slightly higher enantioselectivity (67% ee) was observed, albeit in 46% yield. For the mononuclear C–N chelating ruthenium variants, it has been argued that precise control of the central chirality at the metal of the catalytically active hydrido complexes having three-legged piano stool geometry could be vital for the asymmetric induction through the hydrogen transfer [16]. The above-mentioned formation of minor diastereomers of hydrido(amine)iridium possibly eroded the ee of the chiral secondary alcohol product. The catalytic results indicate that the asymmetric dinuclear complex containing bis(azairidacycle) substructure can behave as a promising bifunctional catalyst for highly efficient transfer hydrogenation, although a redoubled effort to design the chiral ligand structure would be required for dramatic improvement in terms of the discrimination of prochiral face of the ketonic substrates.

O 5 cat, 0.5 mol% OH O OH KOC(CH3)3, 0.6 mol% CH + CH + 3 2-propanol S 3

[ketone] = 0.1 M in 2-propanol 30 °C, 1 h; 60% yield, 60% ee –30 °C, 12 h; 46% yield, 67% ee Scheme 9. Asymmetric transfer hydrogenation of acetophenone in 2-propanol catalyzed by 5.

3. Materials and Methods 3.1. General Information All manipulations of oxygen and moisture-sensitive materials were performed under a purified argon atmosphere using standard Schlenk techniques. Solvents were purchased from Kanto Chemical Co., Inc. (Tokyo, Japan) and dried by refluxing over sodium benzo- phenone ketyl (THF, 1,4-dioxane, and diethyl ether), P2O5 (CH3CN and CH2Cl2), or CaH2 (2-propanol, pentane), and distilled under argon before use. Ethyl acetate and chloroform- d1 was used as delivered. Dichloromethane-d2 was degassed by three freeze–pump–thaw cycles and purified by trap-to-trap distillation after being dried with P2O5. Acetophenone

Molecules 2021, 26, 1165 7 of 12

Figure 2. Selected 1H NMR spectrum of a streoisomeric mixture of hydridoiridium generated from 6 with 2-propanol.

2.3. Catalytic Application to the Asymmetric Transfer Hydrogenation of Acetophenone in 2-Propanol Based on the smooth formation of amidoiridium and hydrido(amine)iridium in the

Molecules 2021, 26, 1165 bis(azairidacycle) system, we further explored its catalytic potential for the asymmetric7 of 12 transfer hydrogenation. The reaction of acetophenone in 2-propanol containing the catalyst precursor 5 with a substrate/iridium ratio of 200 at 30 °C proceeded to give (S)-1- phenylethanol in 60% yield with a moderate ee of 60% after 1 h (Scheme 9). When the ◦ reductionreduction was carried out at −3030 °CC for for 12 12 h, h, a a slightly slightly high higherer enantioselectivity enantioselectivity (67% (67% ee) was observed, albeitalbeit inin 46% 46% yield. yield. For For the th mononucleare mononuclear C–N C–N chelating chelating ruthenium ruthenium variants, variants,it has it been has arguedbeen argued that precise that precise control control of the centralof the central chirality chirality at the metal at the of metal the catalytically of the cat- alyticallyactive hydrido active complexes hydrido complexes having three-legged having three-legged piano stool piano geometry stool could geometry be vital could for thebe vitalasymmetric for the inductionasymmetric through induction the hydrogen through transferthe hydrogen [16]. The transfer above-mentioned [16]. The above-men- formation tionedof minor formation diastereomers of minor of diastereomers hydrido(amine)iridium of hydrido(amine)iridium possibly eroded possibly the ee of eroded the chiral the eesecondary of the chiral alcohol secondary product. alcohol The catalyticproduct. resultsThe catalytic indicate results that indicate the asymmetric that the asymmet- dinuclear riccomplex dinuclear containing complex bis(azairidacycle) containing bis(azairidacycle) substructure can substructure behave as acan promising behave as bifunctional a promis- ingcatalyst bifunctional for highly catalyst efﬁcient for transferhighly efficient hydrogenation, transfer hydrogenation, although a redoubled although effort a redoubled to design effortthe chiral to design ligand the structure chiral ligand would structure be required would for be dramatic required improvement for dramatic in improvement terms of the indiscrimination terms of the discrimination of prochiral face ofof prochiral the ketonic face substrates. of the ketonic substrates.

O 5 cat, 0.5 mol% OH O OH KOC(CH3)3, 0.6 mol% CH + CH + 3 2-propanol S 3

[ketone] = 0.1 M in 2-propanol 30 °C, 1 h; 60% yield, 60% ee –30 °C, 12 h; 46% yield, 67% ee

Scheme 9. AsymmetricAsymmetric transfer transfer hydrogenation of ac acetophenoneetophenone in 2-propanol catalyzed by 5.

3. Materials Materials and and Methods Methods 3.1. General General Information Information All manipulations manipulations of oxygen oxygen and and moisture-sensitive moisture-sensitive materials were performed under a purified purified argon argon atmosphere atmosphere using standard Schlenk techniques. Solvents were purchased fromfrom Kanto Kanto Chemical Chemical Co., Co., Inc. Inc. (Tokyo, (Tokyo, Japan) Japan) and and dried dried by by refluxing refluxing over over sodium sodium benzo- ben- phenonezophenone ketyl ketyl (THF, (THF, 1,4-dioxane, 1,4-dioxane, and and diethyl diethyl ether), ether), P2O P5 (CH2O5 3(CHCN 3andCN CH and2Cl CH2), 2orCl CaH2), or2 (2-propanol,CaH2 (2-propanol, pentane), pentane), and distilled and distilledunder argon under before argon use. before Ethyl acetate use. Ethyl and chloroform- acetate and dchloroform-1 was used das1 wasdelivered. used as Dichloromethane- delivered. Dichloromethane-d2 was degassedd2 was by degassedthree freeze–pump–thaw by three freeze– cyclespump–thaw and purified cycles by and trap-to-trap purified by distillation trap-to-trap after distillation being dried after with being P2O dried5. Acetophenone with P2O5. Acetophenone was purchased from Kanto Chemical Co., Ltd. (Tokyo, Japan), degassed, and stored under argon atmosphere. The other reagents were purchased from Sigma- Aldrich Co. LLC. (St. Louis, MO, USA), Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan), Nacalai Tesque Inc. (Kyoto, Japan) and FUJIFILM Wako Pure Chemical Corporation (Osaka, Japan), and used as delivered. The starting Ir complex, [Cp*IrCl2]2 [49], and Ni and Pd catalysts such as NiCl2 (dppe) [50] were prepared according to the procedures described in the literature with modifications. 1H and 13C{1H} NMR spectra were recorded on a JEOL JNM-LA300 and JNM-ECX400 spectrometers (JEOL Ltd., Tokyo, Japan) at around 25 ◦C unless otherwise noted. The NMR chemical shifts were referenced to an external tetramethylsilane signal (0.0 ppm) by using the signals of residual proton impurities in the deuterated solvents for 1H and 13C{1H} NMR. ESI-MS was acquired with a JEOL JMS-T100LC spectrometer (JEOL Ltd., Tokyo, Japan). Analytical gas chromatography was performed with a Shimadzu GC-17A gas chromatograph equipped with an INNOWAX capillary column (30 m × 0.25 mm i.d.) purchased from Agilent Technologies (Santa Clara, CA, USA). High performance liquid chromatography (HPLC) analysis was performed using a system comprised of a JASCO column oven: CO-1565, a low-pressure gradient unit: LG-1580-02, a pump: PU-1580, a degasser: DG 1580-53, and a UV/VIS detector: UV- 1570. Analytical chiral HPLC was performed on a Chiralcel OD column (4.6 mm × 25 cm) purchased from Daicel Chemical Industries (Osaka, Japan), Ltd. with hexane/2-propanol (95/5) as the eluent where baseline separation was obtained. Molecules 2021, 26, 1165 8 of 12

3.2. Synthesis of 2,20-Bis(aminomethyl)-1,10-Binaphthyl 3.2.1. Synthesis of (S)-1,10-Binaphthalene-2,20-Bis(trifluoromethanesulfonate) (2) 0 To a solution of (S)-1,1 -bi-2-naphthol (2.86 g, 10.0 mmol) in CH2Cl2 (75 mL) was added pyridine (3.16 g, 40.0 mmol), which was followed by a dropwise addition of a solution ◦ of (CF3SO2)2O (6.78 g, 24.0 mmol) in CH2Cl2 (25 mL) at 0 C. After stirring the reaction mixture at room temperature for 1 h, an aqueous solution of 3N HCl was added and stirred for 30 min. The mixture was neutralized by a saturated aqueous solution of NaHCO3, and the organic layer was separated and washed with water and brine. The organic layer containing the product was dried over MgSO4 and concentrated under reduced pressure. Purification by flash chromatography on a silica gel afforded 2 (5.43 g, 99%; Figures S1 1 and S2, In the Supplementary Materials) as a white powder. H NMR (399.8 MHz, CDCl3, 3 3 4 RT): δ 7.26 (d, JHH = 9.1 Hz, 2H; C10H6), 7.41 (ddd, JHH = 7.0 Hz, 7.4 Hz, JHH = 1.2 Hz, 3 4 3 2H; C10H6), 7.58 (ddd, JHH = 6.9 Hz, 7.2 Hz, JHH = 1.2 Hz, 2H; C10H6), 7.62 (d, JHH = 3 3 9.2 Hz, 2H; C10H6), 8.00 (d, JHH = 8.3 Hz, 2H; C10H6), 8.14 (d, JHH = 9.2 Hz, 2H; C10H6). 13 1 1 C{ H} NMR (100.5 MHz, CDCl3, RT): δ 118.2 (q, JCF = 320 Hz, OSO2CF3), 119.4, 123.5, 19 126.8, 127.4, 128.0, 128.4, 132.1, 132.4, 133.2, 145.5 (C10H6). F NMR (376.2 MHz, CDCl3, RT): δ –74.5 (OSO2CF3).

3.2.2. Catalytic Dicyanation of 2 The Schlenk tube containing ditriflate 2 (1.65 g, 3.00 mmol), 1,2-bis(diphenylphosphino) ethane (DPPE; 120 mg, 0.30 mmol), [1,2-bis(diphenylphosphino)ethane]dichloridonickel (163 mg, 0.30 mmol), zinc powder (58.9 mg, 0.90 mmol), and potassium cyanide (430 mg, 6.60 mmol) was flushed with Ar and a deoxygenated DMF (3 mL) was added via syringe. The reaction mixture was stirred under reflux conditions for 24 h. Then, the solvent was removed in vacuo, and ethyl acetate (100 mL) was added to the residue. The resulting mixture was washed with H2O (100 mL × 2) and brine (10 mL), and then dried over anhydrous MgSO4. After evaporation of the organic layer, the resulting material was dissolved in CH2Cl2, and the solution was filtered through a Florisil column. Subsequent purification by flash chromatography on a silica gel afforded (S)-1,10-binaphthalene-2,20-dicarbonitrile 1 3 (799.5 mg, 87%; Figure S3) as white microcrystals. H NMR (399.8 MHz, CDCl3, RT): δ 3 4 3 4 7.16 (dd, JHH = 8.6 Hz, JHH = 0.9 Hz, 2H; C10H6), 7.43 (ddd, JHH = 7.0 Hz, 8.5 Hz, JHH 3 4 = 1.2 Hz, 2H; C10H6), 7.66 (ddd, JHH = 6.7 Hz, 8.3 Hz, JHH = 0.9 Hz, 2H; C10H6), 7.84 (d, 3 3 3 JHH = 8.5 Hz, 2H; C10H6), 8.03 (d, JHH = 8.2 Hz, 2H; C10H6), 8.13 (d, JHH = 8.3 Hz, 2H; 13 1 C10H6). C{ H} NMR (100.5 MHz, CDCl3, RT): δ 117.5 (ArCN), 111.5, 126.4, 126.8, 128.5, 128.7, 129.2, 130.3, 131.8, 134.8, 140.5 (C10H6).

3.2.3. Reduction of 3 Potassium borohydride (1.73 g, 32 mmol), Raney Ni (470 mg), and 10 mL of dry ethanol were placed in a 20 mL Schlenk tube; then, 3 (608 mg, 2.00 mmol) was added while stirring. After stirring vigorously at 50 ◦C for 3 h, the reaction mixture was ﬁltered through a pad of Celite. The solvent was removed in vacuo, and CH2Cl2 was added to the residue. The solution was washed with water. After evaporation of the organic layer, the resulting material was dissolved in ethyl acetate. The amine product was extracted by 1N HCl into the aqueous layer, as the HCl salt form. The aqueous layer was neutralized by 1N NaOH and extracted with diethyl ether. The organic layer was dried over anhydrous Na2SO4. Removal of the solvent under reduced pressure gave the diamine product, 1 (518.2 mg, 1 83%) as a pale yellow oil. H NMR (399.8 MHz, CDCl3, RT): δ 3.48 (d, 2H; CH2NH2), 3.54 3 3 (d, 2H; CH2NH2), 7.07 (d, JHH = 8.5 Hz, 2H; C10H6), 7.20 (dd, JHH = 7.0 Hz, 8.0 Hz, 2H; 3 3 C10H6), 7.41 (dd, JHH = 7.3 Hz, 7.7 Hz, 2H; C10H6), 7.72 (d, JHH = 8.5 Hz, 2H; C10H6), 3 3 13 1 7.91 (d, JHH = 8.3 Hz, 2H; C10H6), 7.99 (d, JHH = 8.5 Hz, 2H; C10H6). C{ H} NMR (100.5 MHz, CDCl3, RT): δ 44.5 (CH2NH2), 125.8, 126.1, 126.5, 126.6, 128.2, 128.7, 132.9, 133.2, 133.6, 139.2 (C10H6). Molecules 2021, 26, 1165 9 of 12

3.3. Double Cyclometalation of 1

To a solution of [Cp*IrCl2]2 (798 mg, 1.00 mmol) in CH3CN (5 mL) was added a solution of 1 (1.0 mmol) in CH3CN. After stirring for 5 min, NaOAc (197 mg, 2.4 mmol) was added to the reaction mixture. Then, the reaction mixture was stirred at 80 ◦C for 15 h. The solvent was removed under reduced pressure. After the reaction mixture was extracted in toluene (10 mL) and filtered through a filter paper, evaporation of the filtrate to dryness gave the product 5 as a yellow powder (831 mg, 0.80 mmol). 1H NMR (399.8 MHz, CDCl3, RT, the major isomer): δ 1.71 (s, 30H; C5(CH3)5), 6.95 (m, 2H; C10H5), 6.99 (m, 2H; C10H5), 7.28 (dd, 2H; C10H5), 7.75 (dd, 2H; C10H5), 7.94 (s, 2H; C10H5). MS(ESI) calcd for + + [C42H48N2ClIr2] [M–Cl] 1001.28, found 1001.25.

3.4. Elimination of HCl from 5 by Treatment of KOC(CH3)3

A stereoisomeric mixture of 5 (0.29 g, 0.28 mmol) and dry KOC(CH3)3 (0.09 g, 0.8 mmol) in CH2Cl2 (3 mL) was stirred at room temperature for 30 min. The reaction mixture was filtered through a pad of Celite under Ar. The solvent was removed under reduced pressure. After the residue was dissolved in diethyl ether, the solution was filtered again through Celite under Ar. Evaporation to dryness of the filtrate gave a dark red-purple 1 powder. The product 6 was dissolved in CD2Cl2 and analyzed by H-NMR spectroscopy. 1 H NMR (399.8 MHz, CD2Cl2, RT): δ 1.94 (br, 4H; CH2), 1.98 (s, 30H; C5(CH3)5), 6.87 (m, 2H; C10H5), 6.95 (m, 2H; C10H5), 7.27 (m, 2H; C10H5), 7.88 (m, 2H; C10H5), 8.22 (br, 4H; NH), 8.67 (s, 2H; C10H5).

3.5. H NMR Observation of the Generation of Hydrido(Amine)Iridium Species from 6 Amidoiridium 6 (95.0 mg, 0.1 mmol) was dissolved in 2-propanol (10 mL) and stirred at room temperature for 2 h. After removal of the solvent under reduced pressure, the resulting solid was washed with pentane and dried under vacuum. The product dissolved in CD2Cl2 was transferred to an NMR tube equipped with a J-Young valve and analyzed by 1H NMR spectroscopy at room temperature.

3.6. Catalytic Asymmetric Transfer Hydrogenation of Acetophenone In 2-Propanol

A 100-mL Schlenk ﬂask was charged with 5 (25.9 mg, 0.025 mmol), KOC(CH3)3 (6.7 mg, 0.06 mmol), durene (111.7 g, 0.83 mmol; an internal standard), and 2-propanol (100 mL) under Ar atmosphere. After the addition of acetophenone (1.20 g, 10 mmol), the reaction mixture was stirred at 30 or –30 ◦C for an appropriate period. The yield of (S)-1-phenylethanol was determined by GC analysis, and the optical purity was determined by HPLC analysis.

4. Conclusions In summary, we have developed a synthetic route to the bifunctional asymmetric catalyst based on bis(azairidacycle). The chiral ligand precursor 1 was concisely synthesized from (S)-BINOL for a total of 72% yield in three steps including the Ni-catalyzed dicyanation of BINOL ditriflate and the subsequent primary amine formation by reduction using Raney-Ni and KBH4. The obtained benzylic diamine could be doubly cyclometalated to give a diastereomeric mixture of chloridoiridium 5, which was convertible to the coordinatively unsaturated amidoiridium in common with the well-defined mononuclear complexes. The metal–ligand cooperation in the amidoiridium complex allowed the smooth transformation into the corresponding hydrido(amine)iridium in 2-propanol. The promotional role of the azairidacycle was also confirmed in the asymmetric transfer hydrogenation of acetophenone, leading to a reasonable enantioselective.ty. Presumably, exquisite control of the diastereoselectivity during formation of the catalytically active hydrido complexes is needed for further improvement of the asymmetric induction ability. These results will be of assistance in the design of new chiral dinuclear catalyst systems with the metal/NH bifunctionality. Molecules 2021, 26, 1165 10 of 12

Supplementary Materials: The following are available online: copies of 1H and 13C{1H} NMR spectra of 1–3 and selected 1H NMR spectrum of 5. Author Contributions: Conceptualization, Y.K. (Yoshihito Kayaki); methodology, Y.S., Y.K. (Yuichi Kawata), S.Y., and Y.K. (Yoshihito Kayaki); validation, Y.S., Y.K. (Yuichi Kawata) S.Y., and Y.K. (Yoshihito Kayaki); formal analysis, Y.S., Y.K. (Yuichi Kawata), S.Y., and Y.K. (Yoshihito Kayaki); investigation, Y.S., Y.K. (Yuichi Kawata), and S.Y.; data curation, Y.S., Y.K. (Yuichi Kawata), S.Y., and Y.K. (Yoshihito Kayaki); writing, Y.S. and Y.K. (Yoshihito Kayaki); project administration, Y.K. (Yoshihito Kayaki); funding acquisition, Y.K. (Yoshihito Kayaki); supervision, T.I. All authors except T.I. have read and agreed to the published version of the manuscript. Funding: This study was funded in part by Grant for Basic Science Research Projects from The Sumitomo Foundation. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: The data presented in this study are available in the Supplemen- tary Materials. Acknowledgments: We are grateful for the support from the Japan Society of Promotion of Science (JSPS) and the Sumitomo Foundation. Conﬂicts of Interest: The authors declare no conﬂict of interest. Sample Availability: Samples of the compounds are not available from the authors.

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