Ru Amido Research Articles

Deeper Mechanistic Insight into Ru Pincer-Mediated Acceptorless Dehydrogenative Coupling of Alcohols: Exchanges, Intermediates, and Deactivation Species

The mechanism of acceptorless dehydrogenative coupling reaction (ADC) of alcohols to esters catalyzed by aliphatic pincer PHNP ruthenium complexes was experimentally studied. Relevant intermediate species involved in the catalytic cycle were isolated and structurally characterized by single-crystal X-ray diffraction studies, and their reactivity (including toward substrates related to the catalytic process) was probed. VT NMR studies unveiled several chemical exchanges connecting the Ru amido hydride, the Ru alkoxide, and the alcohol substrate. Under catalytic conditions, in situ IR spectroscopy monitoring demonstrated the production of ester via aldehyde as intermediate. A Tishchenko-like pathway is proposed as the main path for the production of ester from aldehyde, involving alkoxide and hemiacetaloxide Ru species (the latter being identified in the reaction mixture by NMR). Catalytic system deactivation under base-free conditions was found to be related to water traces in the reaction medium (either a...

The Mechanism of Acceptorless Amine Double Dehydrogenation by N,N,N-Amide Ruthenium(II) Hydrides: A Combined Experimental and Computational Study

A detailed mechanistic analysis of the acceptorless double dehydrogenation of primary amines to form nitriles by HRu(bMepi)(PPh3)2 (1, bMepi = 1,3-bis(6′-methyl-2′-pyridylimino)isoindolate) is presented. The presence of the ortho-CH3 substituents on bMepi is critical for amine dehydrogenation, and no catalysis was observed with HRu(bpi)(PPh3)2 (1-bpi, bpi = 1,3-bis(2′-pyridylimino)isoindolate). Outer-sphere, inner-sphere, and hemilabile pathways were evaluated through ligand substitution and kinetic studies, catalyst modifications, and computational analysis. We propose an inner-sphere mechanism in which a Ru–hydride is protonated by coordinated amine followed by H2 release, which forms a Ru–amido intermediate. The stability of Ru–amido species was evaluated through NBO, AIM, and NCI analyses, revealing steric pressure as well as weak noncovalent interactions between the coordinated amido nitrogen atom and the ortho-alkyl substituents, and these interactions impact the overall thermodynamic profile for am...

Unravelling the Mechanism of the Asymmetric Hydrogenation of Acetophenone by [RuX2(diphosphine)(1,2-diamine)] Catalysts

The mechanism of catalytic hydrogenation of acetophenone by the chiral complex trans-[RuCl2{(S)-binap}{(S,S)-dpen}] and KO-t-C4H9 in propan-2-ol is revised on the basis of DFT computations carried out in dielectric continuum and the most recent experimental observations. The results of these collective studies suggest that neither a six-membered pericyclic transition state nor any multibond concerted transition states are involved. Instead, a hydride moiety is transferred in an outer-sphere manner to afford an ion-pair, and the corresponding transition state is both enantio- and rate-determining. Heterolytic dihydrogen cleavage proceeds neither by a (two-bond) concerted, four-membered transition state, nor by a (three-bond) concerted, six-membered transition state mediated by a solvent molecule. Instead, cleavage of the H-H bond is achieved via deprotonation of the η(2)-H2 ligand within a cationic Ru complex by the chiral conjugate base of (R)-1-phenylethanol. Thus, protonation of the generated (R)-1-phenylethoxide anion originates from the η(2)-H2 ligand of the cationic Ru complex and not from NH protons of a neutral Ru trans-dihydride complex, as initially suggested within the framework of a metal-ligand bifunctional mechanism. Detailed computational analysis reveals that the 16e(-) Ru amido complex [RuH{(S)-binap}{(S,S)-HN(CHPh)2NH2}] and the 18e(-) Ru alkoxo complex trans-[RuH{OCH(CH3)(R)}{(S)-binap}{(S,S)-dpen}] (R = CH3 or C6H5) are not intermediates within the catalytic cycle, but rather are off-loop species. The accelerative effect of KO-t-C4H9 is explained by the reversible formation of the potassium amidato complexes trans-[RuH2{(S)-binap}{(S,S)-N(K)H(CHPh)2NH2}] or trans-[RuH2{(S)-binap}{(S,S)-N(K)H(CHPh)2NH(K)}]. The three-dimensional (3D) cavity observed within these molecules results in a chiral pocket stabilized via several different noncovalent interactions, including neutral and ionic hydrogen bonding, cation-π interactions, and π-π stacking interactions. Cooperatively, these interactions modify the catalyst structure, in turn lowering the relative activation barrier of hydride transfer by ~1-2 kcal mol(-1) and the following H-H bond cleavage by ~10 kcal mol(-1), respectively. A combined computational study and analysis of recent experimental data of the reaction pool results in new mechanistic insight into the catalytic cycle for hydrogenation of acetophenone by Noyori's catalyst, in the presence or absence of KO-t-C4H9.

C–F Bond Breaking through Aromatic Nucleophilic Substitution with a Hydroxo Ligand Mediated via Water Bifunctional Activation

Abstract Transformation of C–F to C–O bond mediated by bifunctional ruthenium and iridium complexes is described. This reaction proceeds through water O–H bond cleavage via metal–ligand cooperation in the newly developed 16e bifunctional ruthenium and iridium complexes bearing chiral (S,S)-C6F5SO2-dpen ligand. The 16e Ru amido complex, [Ru{(S,S)-Pfbsdpen}(η6-hmb)] (1a), readily reacted with water at room temperature producing oxometallacyclic compound, (R)-[Ru{κ3(N,N′,O)-(S,S)-OC6F4SO2dpen}(η6-hmb)] (3aR), as a result of bifunctional water activation followed by ortho-oxometallation via SNAr. Complex 3aR can be prepared either from 1a or, more conveniently from its 18e chlorido precursor, complex (R)-[RuCl{(S,S)-Pfbsdpen}(η6-hmb)]. On the contrary, the 16e Ir amido complex, [Cp*Ir{(S,S)-Pfbsdpen}] (2), is kinetically stable toward water at room temperature. Oxometallacyclic compound (R)-[Cp*Ir{κ3(N,N′,O)-(S,S)-OC6F4SO2dpen}] (4R) was prepared in high yield by the reaction of [Cp*IrCl2]2 with 2 equiv of (S,S)-Pfbsdpen in the presence of KOH under reflux in THF. In either case 3R or 4R is obtained as a single diastereomer, the structure of which has been determined by single-crystal X-ray diffraction studies in solid state and NMR-analysis in solution. Reaction mechanism was studied by NMR spectroscopy combined with continuum solvent reaction-field density functional theory (DFT) analysis. Experimental studies showed that diastereoselective oxocyclometallation 1a → 3aR proceeds at temperatures >0 °C in a stepwise manner through the detectable intermediate, hydroxo complex (R)-[Ru(OH){(S,S)-Pfbsdpen}(η6-hmb)] (6aR), which exists in equilibrium with less-populated diastereomer (S)-[Ru(OH){(S,S)-Pfbsdpen}(η6-hmb)] (6aS) in 10:1 ratio at −80 °C in CD2Cl2. Computational analysis essentially explains the diastereoselectivity in this reaction via a significant difference in the stabilities of the corresponding transition states: although diastereomers 6aR and 6aS are in equilibrium via complex 1a, only 6aR is transformed into 3aR via rate-determining Meisenheimer-type transition state.

Bifunctional Ru Amido Catalyzed Conjugate Addition to Cyclic Enones

Bifunctional Ru Amido Catalyzed Conjugate Addition to Cyclic Enones

A practical asymmetric conjugate addition to cyclic enones with chiral bifunctional Ru amido catalysts

A practical asymmetric C–C bond formation to synthetically useful β-chiral cyclic ketones (>99% ee) using bifunctional chiral amido Ru catalysts under an S/C=1000, the highest ratio achieved so far in the literature for this class of reactions, is described. The catalytic reactivity decreases in the order of Ru(Msdpen)(hmb) > Ru(Pfbsdpen)(hmb) > Ru(Tsdpen)(hmb) > Ru(PMsdpen)(hmb), where Ru(Pfbsdpen)(hmb) is a newly developed chiral bifunctional catalyst. Complex Ru(Msdpen)(hmb) was identified as the best in terms of reactivity and enantioface selectivity, whereas Ru(PMsdpen)(hmb) gave unsatisfactory results. An importance of the NH proton in the bifunctional catalyst for determining the enantioselectivity has been experimentally demonstrated. Valuable information for the reaction mechanism was accumulated.

ChemInform Abstract: Oxo‐Tethered Ruthenium(II) Complex as a Bifunctional Catalyst for Asymmetric Transfer Hydrogenation and H2 Hydrogenation.

Newly developed oxo-tethered Ru amido complexes (R,R)-1 and their HCl adducts (R,R)-2 exhibited excellent catalytic performance for both asymmetric transfer hydrogenation and the hydrogenation of ketonic substrates under neutral conditions without any cocatalysts to give chiral secondary alcohols with high levels of enantioselectivity.

Oxo-Tethered Ruthenium(II) Complex as a Bifunctional Catalyst for Asymmetric Transfer Hydrogenation and H2 Hydrogenation

Newly developed oxo-tethered Ru amido complexes (R,R)-1 and their HCl adducts (R,R)-2 exhibited excellent catalytic performance for both asymmetric transfer hydrogenation and the hydrogenation of ketonic substrates under neutral conditions without any cocatalysts to give chiral secondary alcohols with high levels of enantioselectivity.

Asymmetric 1,4‐Addition of β‐Keto Esters to Cyclic Enones Catalyzed by Ru Amido Complexes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Reactions of (PCP)Ru(CO)(NHPh)(PMe3) (PCP = 2,6-(CH2PtBu2)2C6H3) with Substrates That Possess Polar Bonds

The Ru(II) amido complex (PCP)Ru(CO)(PMe(3))(NHPh) (1) (PCP = 2,6-(CH(2)P(t)Bu(2))(2)C(6)H(3)) reacts with compounds that possess polar C=N, C triple bond N, or C=O bonds (e.g., nitriles, carbodiimides, or isocyanates) to produce four-membered heterometallacycles that result from nucleophilic addition of the amido nitrogen to an unsaturated carbon of the organic substrate. Based on studies of the reaction of complex 1 with acetonitrile, the transformations are suggested to proceed by dissociation of trimethylphosphine, followed by coordination of the organic substrate and then intramolecular N-C bond formation. In the presence of ROH (R = H or Me), the fluorinated amidinate complex (PCP)Ru(CO)(N(Ph)C(C(6)F(5))NH) (6) reacts with excess pentafluorobenzonitrile to produce (PCP)Ru(CO)(F)(N(H)C(C(6)F(5))NHPh) (7). The reaction with MeOH also produces o-MeOC(6)F(4)CN (>90%) and p-MeOC(6)F(4)CN (<10%). Details of the solid-state structures of (PCP)Ru(CO)(F)(N(H)C(C(6)F(5))NHPh) (7), (PCP)Ru(CO)[PhNC{NH(hx)}N(hx)] (8), (PCP)Ru(CO){N(Ph)C(NHPh)O} (9), and (PCP)Ru(CO){OC(Ph)N(Ph)} (10) are reported.

Asymmetric 1,4-addition of β-keto esters to cyclic enones catalyzed by Ru amido complexes

Well-defined Ru amido complexes effected asymmetric Michael addition of β-keto esters to 2-cyclopenten-1-one to give quantitatively the corresponding Michael adducts with excellent ee although with a 1:1 diastereomer ratio. The stereochemical outcome of the reaction was significantly influenced by the structures of the catalysts and the structures of the β-keto esters; the ee value reaching up to 97%.

Catalytic Enantioselective Michael Addition of 1,3‐Dicarbonyl Compounds to Nitroalkenes Catalyzed by Well‐Defined Chiral Ru Amido Complexes.

Well-defined chiral Ru amido complexes promoted asymmetric Michael addition of 1,3-dicarbonyl compounds including malonates, beta-keto esters, and 1,3-diketones to nitroalkenes to give the corresponding adducts with excellent ees and in excellent yields.

Catalytic enantioselective Michael addition of 1,3-dicarbonyl compounds to nitroalkenes catalyzed by well-defined chiral ru amido complexes.

Well-defined chiral Ru amido complexes promoted asymmetric Michael addition of 1,3-dicarbonyl compounds including malonates, beta-keto esters, and 1,3-diketones to nitroalkenes to give the corresponding adducts with excellent ees and in excellent yields.

Reactivity of amido ligands on a dinuclear Ru(II) center: formation of imido complexes and C-N coupling reaction with alkyne.

Treatment of a dinuclear Ru(II) amido complex [Cp*Ru(mu2-NHPh)]2 (Cp* = eta5-C5Me5) with small organic substrates including CO, tert-butyl isocyanide, a sulfur ylide Ph2S=CH2, and diphenylacetylene resulted in an unexpected disproportionation reaction of the bridging amido ligands to produce a free amine and a series of imido-bridged diruthenium complexes [(Cp*Ru)2(mu2-L)(mu2-NPh)] (L = CO, t-BuNC, CH2). In the case of diphenylacetylene, the bridging imido ligand underwent subsequent coupling reaction with the coordinated alkyne to form an iminoalkenyl complex [(Cp*Ru)2(mu2-PhNCPhCPh)].

Asymmetric Michael Reactions of α‐Substituted Acetates with Cyclic Enones Catalyzed by Multifunctional Chiral Ru Amido Complexes

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric Michael reactions of α-substituted acetates with cyclic enones catalyzed by multifunctional chiral Ru amido complexes

Well-defined 16-electron chiral Ru amido complexes, Ru[( R, R)-diamine](η 6-arene), efficiently catalyze asymmetric Michael additions of Michael donors to cyclic enones to give adducts in high yields and with excellent ee’s. β-Ketoesters or nitroacetate as Michael donors react with 2-cyclopentenone in toluene or t-butyl alcohol containing the Ru amido catalyst (S/C=50) to afford the Michael adduct in 99% yield and with up to 92% ee. The outcome of the reaction was delicately influenced by the structures of the diamine and arene ligands as well as reaction conditions.

Enantioselective Michael Reaction Catalyzed by Well‐Defined Chiral Ru Amido Complexes: Isolation and Characterization of the Catalyst Intermediate, Ru Malonato Complex Having a Metal—Carbon Bond.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Octahedral Ru(II) amido complexes TpRu(L)(L')(NHR) (Tp = hydridotris(pyrazolyl)borate; L = L' = P(OMe)3 or PMe3 or L = CO and L' = PPh3; R = H, Ph, or tBu): synthesis, characterization, and reactions with weakly acidic C-H bonds.

The octahedral Ru(II) amine complexes [TpRu(L)(L')(NH(2)R)][OTf] (L = L' = PMe(3), P(OMe)(3) or L = CO and L' = PPh(3); R = H or (t)Bu) have been synthesized and characterized. Deprotonation of the amine complexes [TpRu(L)(L')(NH(3))][OTf] or [TpRu(PMe(3))(2)(NH(2)(t)Bu)][OTf] yields the Ru(II) amido complexes TpRu(L)(L')(NH(2)) and TpRu(PMe(3))(2)(NH(t)Bu). Reactions of the parent amido complexes or TpRu(PMe(3))(2)(NH(t)Bu) with phenylacetylene at room temperature result in immediate deprotonation to form ruthenium-amine/phenylacetylide ion pairs, and heating a benzene solution of the [TpRu(PMe(3))(2)(NH(2)(t)Bu)][PhC(2)] ion pair results in the formation of the Ru(II) phenylacetylide complex TpRu(PMe(3))(2)(C[triple bond]CPh) in >90% yield. The observation that [TpRu(PMe(3))(2)(NH(2)(t)Bu)][PhC(2)] converts to the Ru(II) acetylide with good yield while heating the ion pairs [TpRu(L)(L')(NH(3))][PhC(2)] yields multiple products is attributed to reluctant dissociation of ammonia compared with the (t)butylamine ligand (i.e., different rates for acetylide/amine exchange). These results are consistent with ligand exchange reactions of Ru(II) amine complexes [TpRu(PMe(3))(2)(NH(2)R)][OTf] (R = H or (t)Bu) with acetonitrile. The previously reported phenyl amido complexes TpRuL(2)(NHPh) [L = PMe(3) or P(OMe)(3)] react with 10 equiv of phenylacetylene at elevated temperature to produce Ru(II) acetylide complexes TpRuL(2)(C[triple bond]CPh) in quantitative yields. Kinetic studies indicate that the reaction of TpRu(PMe(3))(2)(NHPh) with phenylacetylene occurs via a pathway that involves TpRu(PMe(3))(2)(OTf) or [TpRu(PMe(3))(2)(NH(2)Ph)][OTf] as catalyst. Reactions of 1,4-cyclohexadiene with the Ru(II) amido complexes TpRu(L)(L')(NH(2)) (L = L' = PMe(3) or L = CO and L' = PPh(3)) or TpRu(PMe(3))(2)(NH(t)Bu) at elevated temperatures result in the formation of benzene and Ru hydride complexes. TpRu(PMe(3))(2)(H), [Tp(PMe(3))(2)Ru[double bond]C[double bond]C(H)Ph][OTf], [Tp(PMe(3))(2)Ru=C(CH(2)Ph)[N(H)Ph]][OTf], and [TpRu(PMe(3))(3)][OTf] have been independently prepared and characterized. Results from solid-state X-ray diffraction studies of the complexes [TpRu(CO)(PPh(3))(NH(3))][OTf], [TpRu(PMe(3))(2)(NH(3))][OTf], and TpRu(CO)(PPh(3))(C[triple bond]CPh) are reported.

Enantioselective Michael reaction catalyzed by well-defined chiral ru amido complexes: isolation and characterization of the catalyst intermediate, ru malonato complex having a metal-carbon bond.

Chiral Ru amido complexes promote asymmetric Michael addition of malonates to cyclic enones, leading to Michael adducts with excellent ee's, in which the chiral Ru amido complexes react with malonates to give isolable catalyst intermediates, chiral Ru malonato complexes bearing a metal bound C-nucleophile.

Ruthenium(II) Anilido Complexes TpRuL2(NHPh): Oxidative 4,4‘-Aryl Coupling Reactions (Tp = Hydridotris(pyrazolylborate); L = PMe3, P(OMe)3, or CO)

Reactions of the Ru(II) amido complexes TpRuL2(NHPh) (L = CO, PMe3, or P(OMe)3) with AgOTf (OTf = trifluoromethanesulfonate) yield the binuclear complexes [TpRuL2NH(C6H4−)]2[OTf]2 along with the Ru(II) amine complexes [TpRuL2(NH2Ph)][OTf] in an approximate 1:1 molar ratio. In these reactions, the two ruthenium fragments are coupled via C−H bond cleavage and C−C bond formation at the para position of anilido ligands. A resonance structure corresponding to Ru(II) metal centers linked by a diimine ligand contributes significantly to the bonding. Evidence for such a contribution comes from the diamagnetic nature of the binuclear complexes and a solid-state X-ray crystallographic study of [TpRu{P(OMe)3}2NH(C6H4−)]2[OTf]2. It is proposed that the coupled products are formed via initial single-electron oxidation followed by C−C bond formation. Variable-temperature NMR spectra of the aryl-coupled complexes are consistent with two geometrical isomers around the rigid HN−C6H4−C6H4NH bridges.