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Examines the complete identification of diastereometric catalyst substrate species in an enantioselective ketone hydrogenation. Solution structure of diastereomer catalyst; Formation of catalyst-alkoxide complexes; Determination of the enantioselective hydrogenation of olefins.

Reaction of [Ru((R)-BINAP)(H)(MeCN)[sub n] (acetone)[sub 3–] [sub n] ](BF[sub 4] ) (where n = 0–3) (2) with 1 equiv of the olefin substrate methyl α-acetamidoacrylate (MAA) in acetone at room temperature immediately generated a mixture (72:28) of two diastereomers of the complex [Ru((R)-BINAP)(MeCN)(MAA(H))](BF[sub 4] ) (3). The olefin–hydride insertion reaction between 2 and MAA to generate 3 was regioselective, with transfer of the hydride to the β-olefinic carbon and transfer of ruthenium to the α-carbon in both diastereomers of 3. The two diastereomers of 3 differ by the absolute configuration at the α-carbon of MAA(H) ((S[sub Cα] )-3 and (R[sub Cα] )-3). The absolute configuration of the major ((S[sub Cα] )-3) diastereomer was determined by X-ray diffraction in conjunction with NMR spectroscopic data. Protonolysis of the ruthenium–carbon bond in 3 and in the methyl α-acetamidocinnamate (MAC) analog ([Ru((R)-BINAP)(MeCN)((S)- MAC(H))](BF[sub 4] ) ((S[sub Cα] )-4)) by addition of 2 equiv HBF[sub 4] ·Et[sub 2] O in CH[sub 2] Cl[sub 2] at room temperature was not stereospecific and did not occur with β-hydride elimination from the methyl or benzyl groups.Key words: ruthenium, BINAP, enantioselective, hydrogenation, catalysis.La réaction du [Ru((R)-BINAP(H)(MeCN)[sub n] (acétone)[sub 3–] [sub n] ](BF[sub 4] ) (dans lequel n = 0–3) (2) avec un équivalent du substrat oléfinique α-acétamidoacétate de méthyle ("MAA"), dans l'acétone, à la température ambiante, conduit immédiatement à la formation d'un mélange (72:28) de deux diastéréomères du complexe [Ru((R)-BINAP(MeCN)("MAA"(H))](BF[sub 4] ) (3). La réaction d'insertion oléfine–hydrure entre 2 et "MAA" pour générer 3 est régiosélective; dans les deux diastéréomères de 3, le transfert de l'hydrure se portant sur le carbone oléfinique β et le transfert de ruthénium sur le carbone α. Les deux diastéréomères de 3 diffèrent par la configuration absolue au niveau du carbone en α du "MAA"(H) ((S[sub Cα] )-3) et ((R[sub Cα] )-3). On a déterminé la configuration absolue du produit principal, le diastéréomère ((S[sub Cα] )-3), par diffraction des rayons X alliée aux données de spectroscopie RMN. La protonolyse de la liaison ruthénium–carbone présente dans le composé 3 et dans son analogue α-acétamidocinnamate de méthyle ("MAC"), le [Ru((R)-BINAP(MeCN)((S)-"MAC"(H))](BF[sub 4] ) ((S[sub Cα] )-4), a été réalisée par addition de deux équivalents de HBF[sub 4] ·Et[sub 2] O, dans du CH[sub 2] Cl[sub 2] , à la température ambiante; cette réaction n'est pas stéréospécifique et elle ne se produit pas par le biais d'une élimination β à partir des groupes méthyle ou benzyle.Mots clés : ruthénium, BINAP, énantiosélective, hydrogénation, catalyseur.[Traduit par la Rédaction] [ABSTRACT FROM AUTHOR]

The article discusses a study which investigates on several catalytic hydrogenations of ketones which reveal an unexpected role of base in the systems. The study conducted several approaches including kinetics and isotope labeling studies, use of nonprotic solvents and the use of model compounds. Researchers concluded that hydrogen addition in the presence of base is turnover limiting because the steady state concentration of amide 5 is low in the process of catalytic hydrogenation.

Abstract: The mechanism of ruthenium-bis(phosphine) catalyzed enantioselective hydrogenation of olefins was examined using [Ru((R)-BINAP)(H)(MeCN) n (sol)3− n ]BF4 (n =0–3, sol=solvent used in reaction) as catalyst. Tiglic and angelic acids were used as standard α,β-unsaturated acid substrates; (Z)-methyl α-acetamidocinnamate and dimethyl itaconate were used as standard α,β-unsaturated ester substrates. Isotopic labeling studies (deuterium scrambling) indicate that two distinct mechanisms are in operation for α,β-unsaturated acids versus α,β-unsaturated esters. In each case, 5-membered metallocycle intermediates are formed via olefin-hydride insertion. The mechanisms, however, deviate primarily in the activation of dihydrogen, which is strongly affected by the nature of the substrate. Hydrogenation of α,β-unsaturated acids proceed via heterolytic cleavage of dihydrogen, whereas hydrogenation of α,β-unsaturated esters proceed via homolytic cleavage of dihydrogen. A full discussion of the mechanisms is presented. [Copyright &y& Elsevier]

High-throughput screening and lab-scale optimization were combined to develop the catalytic system trans-RuCl2((S,S)-skewphos)((R,R)-dpen), 2-PrONa, and 2-PrOH. This system hydrogenates functionalized α-phenoxy and related amides at room temperature under 4 atm H2 pressure to give chiral alcohols with up to 99% yield and in greater than 99% enantiomeric excess via dynamic kinetic resolution. [ABSTRACT FROM AUTHOR]

Mono- or dideprotonation at the N-H groups of the Noyori ketone hydrogenation catalyst trans-[RuH2((R)-BINAP)((R,R)-dpen)] (1a) yields trans-M[RuH2((R,R)-HNCH(Ph)CH(Ph)NH2)((R)-BINAP)], where M = K+(8-K) or Li+ (8-Li), or trans-M2[RuH2((R,R)-HNCH(Ph)CH(Ph)NH)((R)-BINAP)], where M = Li+ (8-M′2), which have unprecedented activity toward the hydrogenation of amide and imide carbonyls at low temperatures in THF-d8. Details of the origins of the enantioselection for the desymmetrization of meso-cyclic imides by hydrogenation with 8-K are also described herein. [ABSTRACT FROM AUTHOR]

The transition state for the metal—ligand bifunctional addition step in Noyori's enantioselective ketone hydrogenation was investigated using intramolecular trapping experiments. The bifunctional addition between the Rn dihydride frans-[Ru((R)-BINAP) (H)2((R,R)-dpen)] and the hydroxy ketone 4-HOCH2C6H4(CO)CH3 at -80 °C exclusively formed the corresponding secondary ruthenium alkoxide trans-[Ru((R)-BINAP) (H) (4-HOCH2C6-H4CH(CH3)O)((R,R)-dpen)]. Combined with the results of control experiments, this observation provides strong evidence for the formation of a partial Ru—O bond in the transition state. [ABSTRACT FROM AUTHOR]

The article focuses on a ruthenium-dihydrogen putative intermediate in ketone hydrogenation. It presents a report of the first direct observation and reactivity study of a cationic, Ru-dihydrogen-hydride compound as a putative intermediate in an asymmetric ketone hydrogenation. The catalyst systems comprised of trans-(bisphosphine)RuCI2(diamine) and a base, developed by Noyori et al., are the most active and selective catalysts for the asymmetric hydrogenation of aryl-ailcyl and related ketones. Turnover numbers in the millions and enantiomeric excesses greater than 99% have been achieved with these catalysts.