No.147 No.147 Bifunctional Molecular Catalysts with Cooperating Amine/Amido Ligands Yoshihito Kayaki and Takao Ikariya* Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1-E4-1 O-okayama, Meguro-ku, Tokyo, 152-8552, Japan E-mail: [email protected] 1. Introduction and a coordinatively saturated hydrido(amine)ruthenium complex are involved in the catalytic cycle as depicted in The chemistry of transition metal-based molecular Figure 1. The amido complex has sufficient Brønsted basicity catalysts has progressed with discoveries of novel catalytic to dehydrogenate readily secondary alcohols including transformations as well as understanding the reaction 2-propanol to produce the hydrido(amine) complex. The NH mechanisms. Particularly, significant efforts have been unit bound to the metal center in the amine complex exhibits continuously paid to develop bifunctional molecular catalysts a sufficiently acidic character to activate ketonic substrates. having the combination of two or more active sites working in During the interconversion between the amido and the amine concert, to attain highly efficient molecular transformation for complexes, the metal/NH moiety cooperatively assists the organic synthesis. We have recently developed metal–ligand hydrogen delivery via a cyclic transition state where H– and cooperating bifunctional catalysts (concerto catalysts), in which H+ equivalents are transferred in a concerted manner from the the non-innocent ligands directly participate in the substrate hydrido(amine) complex to the C=O linkage or from 2-propanol activation and the bond formation. The concept of bifunctional to the amido complex without direct coordination to the metal molecular catalysis is now an attractive and general strategy to center (outer-sphere mechanism). This unique concept of the realize effective molecular transformation.1 bifunctional transition metal based-molecular catalysts leads to In 1995, Noyori and co-workers reported an unprecedented reactions with high rates and excellent stereoselectivies because effect of diamine ligands on the enantioselective hydrogenation the reactions proceed through a tight-fitting assembly of the of simple aromatic ketones with BINAP-Ru(II) system reactants and chiral catalysts. [BINAP = 2,2’-bis(diphenylphosphino-1,1’-binaphthyl)].2 A Figure 2 lists some representative examples of well-defined combination of RuCl2[(S)-binap](dmf)n, chiral 1,2-diamine, bifunctional molecular catalysts recently developed in our group. and KOH showed an extremely high activity toward ketone The concept of the chiral bifunctional η6-arene–Ru complexes, hydrogenation than the classical BINAP–Ru catalyst. RuH(Tsdpen)(η6-arene), [Tsdpen = N-(p-toluenesulfonyl)-1,2- Subsequently, a prototype of a conceptually new phosphine- diphenylethylenediamine] has been successfully extended to free Ru catalyst bearing N-sulfonylated 1,2-diamines as analogous Cp*Rh and Ir complexes, Cp*MH(Tsdpen) [Cp* = 5 4 chiral ligands was developed for highly efficient asymmetric η -C(CH3)5, M = Rh, Ir]. In addition to the N-sulfonylated transfer hydrogenation of ketones.3 Detailed experimental and diamine complexes, group 8 and 9 metal complexes with theoretical analyses of the real catalysts revealed that both an diamines (N–N),5 aminophosphines (P–N),6 aminoethanethiols amidoruthenium complex having a square-planar geometry (S–N),7 and o-aminomethylphenyl (C–N)8 ligands have been Ts Rn R N Ru N R H Rn H H Ar amine hydrido Ts δ+ δ– O complex O Ru C δ+ N H δ– N O δ– H H Hδ+ Ar H OH OH Ts A possible transition state Rn R N Ru R N H amido complex Figure 1. Concept of Concerto molecular catalysis: Interconversion of the amido and the amine hydrido Ru complex via a possible six-membered transition state. 2 No.147 No.147 extensively developed as the bifunctional molecular catalyst their unique hydrogenation/dehydrogenation mechanism via bearing the metal/NH effect. dearomatization. Fujita and Yamaguchi have designed Cp*Ir complexes (E)13 having 2-hydroxypyridine and pyridonate As related bifunctional catalysts studied by other research ligands which efficiently promote dehydrogenation of secondary groups, Figure 3 represents several group 8 and 9 metal alcohols by the aid of the acidic OH function. Kitamura and complexes in which protic functional groups on the ancillary Tanaka demonstrated that the acidic nature of 2-quinoline ligands works cooperatively with the metal center to catalyze carboxylic acid on a CpRu fragment (F) effects a C–O bond hydrogenation, transfer hydrogenation, and so on. The Zhang’s activation of allyl alcohols to afford allyl ethers.14 (A)9 and Grützmacher’s catalysts (B)10 having tridentate protic amine ligands can help the H+/H– transfer in a similar manner This article focuses on the outline of our recent progress to our bifunctional catalysts. The Shvo’s catalyst (C)11 can in the bifunctional molecular catalysts based on the metal/ release the catalytically active species, cyclopentadienyl and NH synergy, and their utilization to asymmetric redox cyclopentadienone complexes, and the OH group plays a transformations and related enantioselective C–C and C–N bond vital role as a proton mediator to promote hydrogen transfer formation reactions. processes. Recently, Milstein developed new PNN pincer complexes (D)12 as highly active redox catalysts and found Ts Ts Ts Ts Rn Rn C6H5 C6H5 N N N N Ru Ru M M N N N C6H5 H N H C6H5 H H H H H H H H H H RuH(Tsdpen)(η6-arene) RuH(Tscydn)(η6-arene) Cp*MH(Tsdpen) Cp*MH(Tscydn) M = Rh, Ir M = Rh, Ir R2 S Rn P N Ru Ru Ru M R N H R N H N N H H R H H H H HH H Cp*RuH(P–N) Cp*RuH(N–N) Cp*MH(C–N) RuH(S–N)(η6-arene) M = Rh, Ir Figure 2. Bifunctional catalysts bearing protic chelate amine ligands. O (A) C6H5 (B) H H N N N H Cl Rh H = HN Ru L N Cl P(C6H5)3 N C6H5 O (C) O O Ph Ph Ph H Ph Ph Ph Ph OH O Ph H Ph Ph Ph Ph Ph Ph Ph Ru Ru Ph Ru + Ru OC H OC CO OC CO OC CO OC H (D) H t t P Bu2 P Bu2 H –H2 N Ru CO N Ru CO H H H2 NEt2 NEt2 + (E) (F) N N Ir Ru HO Cl Cl O O solv. H Figure 3. Related examples of metal-ligand cooperating catalysts having protic functional moiety. 3 No.147 No.147 2. Asymmetric Transfer Hydrogenation Using nitro, azide, and chloro groups as well as heteroaromatic Bifunctional Catalysts1c rings and the alkyne linkage,1c as summarized in Figure 4. Carbon–nitrogen double bonds are also reducible with a mixture In general, 2-propanol can be used as a safe, nontoxic, of formic acid and triethylamine containing chiral Ru or Rh environmentally friendly hydrogen source. Although the catalysts to the corresponding amines with a high level of asymmetric reduction in 2-propanol gives satisfactory results, enantiomeric excesses.16 an inherent drawback of the hydrogen transfer reaction is its reversibility, leading to limited conversion determined by A series of Cp*Ru(P–N) complexes bearing the protic thermodynamic factors of the system and the deterioration of phosphine-amine chelating ligands also serve as highly efficient enantiomeric purity of the products upon a long exposure of catalysts for transfer hydrogenation as shown in Figure 5. the reaction mixture to the catalyst. On the other hand, formic Based on the reversible hydrogen transfer mechanism via acid is amenable to the asymmetric reduction in an irreversible interconversion between both the amido and amine complexes, fashion leading to 100% conversion.15 the redox process can be successfully applied to rapid Asymmetric reduction of simple aromatic ketones with racemization of chiral alcohols17 as well as regioselective a mixture of formic acid and triethylamine containing the oxidative transformation of diols to lactones using acetone.18 bifunctional catalyst is characterized by high efficiency in terms A chiral Cp*Ru(P–N) complex accomplishes enantioselective of activity, selectivity, wide substrate scope, and practicability. isomerization of allylic alcohols to β-substituted ketones, and The bifunctional hydrido(amine)-Ru complex is coordinatively the following ring-closing metathesis affords (R)-muscone19 saturated, and the catalyst system tolerates amino, ester, cyano, with a moderate ee. OH O OH C6H5 C6H5 99% yield, 96% ee OH C6H5 89% yield, 99% ee >99% yield, 97% ee OH OH X C6H5 C6H5 Ts OH X = CN, N , NO R Rn 3 2 N 67–100% yield, 95–98% ee 78% yield, 95% ee Ru R N H H H OH HCOOH/N(C2H5)3 OH C6H5 or (CH3)2CHOH Cl C H 6 5 C6H5 OH 100% yield Cp*RhCl[(S,S)-Tsdpen] dl:meso = 98.6:1.4. 99% ee >99% yield, 98% ee OH O OH N OH C6H5 n OC2H5 O n = 1, 94% yield, 93% ee n = 3, 99% yield, 95% ee 97% yield, 95% ee >99% yield, 98% ee Figure 4. Asymmetric transfer hydrogenation of ketones with chiral Ru and Rh catalysts. OH Cp*RuCl(P–N) OH KO tBu Ph2 toluene P Ru N Cl H O 2 Cp*RuCl(P–N) ArCH2 ArCH2 Cp*RuCl(P–N) OH KO tBu O OH toluene ArCH2 ArCH2 Cp*RuCl(P–N)* OH O KO tBu Ph2 toluene * 8 8 P 74% ee Ru O NH Cl * Cp*RuCl(P–N)* muscone Figure 5. Hydrogen transfer reactions with Cp*Ru(P­–N) catalysts. 4 No.147 No.147 3. Catalytic Hydrogenation of Polar Substrates The Cp*Ru(P–N) catalysts also promote the hydrogenation with Bifunctional Catalysts6 of esters and carboxamides to give alcohols or amines under more forcing conditions.23b This hydrogenation procedure will Since we reported an effect of alcoholic solvent facilitating provide a powerful alternative method for classical reduction the heterolytic cleavage of H2 bound to the 16-electron using stoichiometric amounts of metal hydride reagents.