(β‐Amino alcohol)(arene)ruthenium(II)‐Catalyzed Asymmetric Transfer Hydrogenation of Functionalized Ketones − Scope, Isolation of the Catalytic Intermediates, and Deactivation Processes

The asymmetric transfer hydrogenation of functionalized ketones with (β-amino alcohol)(arene)RuII catalysts using 2-propanol as the hydrogen source has been studied. The structure of the catalyst has been systematically screened using a wide variety of [(η6-arene)RuCl2]2 complexes and β-amino alcohols R1CH(OH)CHR2NHR3, some of which were specifically designed for optimized performance, e.g. (1S,2R)-N-(4-biphenylmethyl)norephedrine (9o). The efficiencies of the catalytic combinations have been evaluated in the reduction of β-oxo esters and ketones bearing heteroatoms at the α-position. The catalyst precursor [{η6-p-cymene}{η2-N,O-(9o)}RuCl] (35), the 16-electron true catalyst [{η6-p-cymene}{η2-N,O-(9o1−)}Ru] (36), and the hydride [{η6-p-cymene}{η2-N,O-(9o)}RuH] (37) involved in the reduction process have been isolated, characterized by NMR and ESI-MS, as well as by X-ray crystallography in the case of 35, and their reactivities have been investigated. The results reveal two general trends regarding this catalytic process: (1) the apparent reaction rate and the enantioselectivity are largely controlled by the nature of the amine functionality of the chiral ligand and the arene ring of the RuII precursor; (2) side reactions occur between the ketone substrate and the active catalytic species that affect the concentration of the latter and consequently the apparent rate; the formation of inactive (β-diketonato)RuII complexes is demonstrated in the case of β-oxo esters.

[1]  M. Hennig,et al.  Synthesis of (R)- and (S)-4-hydroxyisophorone by ruthenium-catalyzed asymmetric transfer hydrogenation of ketoisophorone , 2000 .

[2]  C. Frost,et al.  Probing subtle ligand effects in the enantioselective transfer hydrogenation of ketones , 2000 .

[3]  Alonso,et al.  2-Azanorbornyl alcohols: very efficient ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of aromatic ketones , 2000, The Journal of organic chemistry.

[4]  Ryoji Noyori,et al.  The Metal−Ligand Bifunctional Catalysis: A Theoretical Study on the Ruthenium(II)-Catalyzed Hydrogen Transfer between Alcohols and Carbonyl Compounds , 2000 .

[5]  H. Schoemaker,et al.  IR spectroscopy as a high-throughput screening-technique for enantioselective hydrogen-transfer catalysts , 2000 .

[6]  A. Heck,et al.  The detection of intermediates in the ruthenium(II) catalysed asymmetric hydrogenation of ketones using electrospray ionisation mass spectrometry , 2000 .

[7]  M. Wills,et al.  Asymmetric Transfer Hydrogenation of a-Amino and a-Alkoxy Substituted Ketones , 1999 .

[8]  A. Mortreux,et al.  Steric effects in the enantioselective transfer hydrogenation of 2-aroylacetates , 1999 .

[9]  H. Schoemaker,et al.  Amino Alcohol Coordination in Ruthenium(II)-Catalysed Asymmetric Transfer Hydrogenation of Ketones , 1999 .

[10]  A. Mortreux,et al.  N-Benzyl-norephedrine derivatives as new, efficient ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of functionalized ketones , 1999 .

[11]  R. Crabtree.  Combinatorial and rapid screening approaches to homogeneous catalyst discovery and optimization , 1999 .

[12]  M. Wills,et al.  Novel catalysts for asymmetric reduction of carbonyl groups , 1999 .

[13]  P. Andersson,et al.  Ru(arene)(amino alcohol)-Catalyzed Transfer Hydrogenation of Ketones: Mechanism and Origin of Enantioselectivity , 1999 .

[14]  T. Ikariya,et al.  A Practical Stereoselective Synthesis of Chiral Hydrobenzoins via Asymmetric Transfer Hydrogenation of Benzils , 1999 .

[15]  M. Wills,et al.  Asymmetric transfer hydrogenation of C=O and C=N bonds , 1999 .

[16]  T. Ikariya,et al.  New Chiral Rhodium and Iridium Complexes with Chiral Diamine Ligands for Asymmetric Transfer Hydrogenation of Aromatic Ketones , 1999 .

[17]  A. Willis,et al.  Bis(acetylacetonato)bis(cyclooctene)ruthenium(II), cis-[Ru(acac)2(η2-C8H14)2]: a synthetic precursor to trans- and cis-bis(acetylacetonato)ruthenium(II) complexes† , 1999 .

[18]  Tomoyuki Abe,et al.  The Half-sandwich Hydride and 16-Electron Complexes of Rhodium and Iridium Containing (1S, 2S)-N-(p-Toluenesulfonyl)-1, 2-diphenylethylenediamine : Relevant to the Asymmetric Transfer Hydrogenation , 1998 .

[19]  Tomoyuki Abe,et al.  Asymmetric Transfer Hydrogenation of Ketonic Substrates Catalyzed by (η5-C5Me5)MCl Complexes (M = Rh and Ir) of (1S,2S)-N-(p-Toluenesulfonyl)-1,2-diphenylethylenediamine , 1998 .

[20]  H. Kagan.  New screening methodologies or combinatorial chemistry applied to asymmetric catalysts , 1998 .

[21]  A. Mortreux,et al.  Ruthenium catalyzed asymmetric transfer hydrogenation of β-ketoesters , 1998 .

[22]  P. Andersson,et al.  (1S,3R,4R)-2-Azanorbornylmethanol, an Efficient Ligand for Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of Ketones. , 1998, The Journal of organic chemistry.

[23]  P. Knochel,et al.  New C2-symmetrical ferrocenyl diamines as ligands for ruthenium catalyzed transfer hydrogenation , 1998 .

[24]  T. Ikariya,et al.  Asymmetric Transfer Hydrogenation of a,-Acetylenic Ketones , 1997 .

[25]  R. Noyori,et al.  Asymmetric Transfer Hydrogenation Catalyzed by Diamine - Iridium(I) Complexes , 1997 .

[26]  M. Wills,et al.  (1R,2S)-(+)-cis-1-Amino-2-indanol: An Effective Ligand for Asymmetric Catalysis of Transfer Hydrogenations of Ketones , 1997 .

[27]  G. Raabe,et al.  Coordinatively Unsaturated Cp*Ru Alkoxo Complexes. 16.1 Addition Products Cp*Ru(acac)L and Solution Equilibria1 , 1997 .

[28]  T. Ikariya,et al.  The Catalyst Precursor, Catalyst, and Intermediate in the RuII‐Promoted Asymmetric Hydrogen Transfer between Alcohols and Ketones , 1997 .

[29]  and Ryoji Noyori,et al.  Asymmetric Transfer Hydrogenation Catalyzed by Chiral Ruthenium Complexes , 1997 .

[30]  R. Noyori,et al.  Ruthenium(II)-Catalyzed Asymmetric Transfer Hydrogenation of Ketones Using a Formic Acid−Triethylamine Mixture , 1996 .

[31]  T. Ikariya,et al.  Amino alcohol effects on the ruthenium(II)-catalysed asymmetric transfer hydrogenation of ketones in propan-2-ol , 1996 .

[32]  T. Ikariya,et al.  Asymmetric Transfer Hydrogenation of Aromatic Ketones Catalyzed by Chiral Ruthenium(II) Complexes , 1995 .

[33]  Joop A. Peters,et al.  Meerwein-Ponndorf-Verley Reductions and Oppenauer Oxidations: An Integrated Approach , 1994 .

[34]  G. Raabe,et al.  [Cp*Ru(acac)] Is Not a Coordinatively Unsaturated, Stable 16‐Valence‐Electron Complex , 1993 .

[35]  R. Noyori,et al.  Enantioselective synthesis of 4-substituted γ-lactones , 1990 .

[36]  J. Brussee,et al.  Synthesis of optically active ethanolamines , 1990 .

[37]  J. Brussee,et al.  Magnesium ion mediated stereospecific formation of N-substituted ethanolamines during reductive amination , 1990 .

[38]  K. Bowden,et al.  Reactions of carbonyl compounds in basic solutions. Part 13. The mechanism of the alkaline hydrolysis of 3-(3-substituted phenoxy)phthalides, -3-methyl-phthalides, -3-phenylphthalides, naphthalides, -3-phenylnaphthalides, and phenanthralides, and of 3-substituted 3-methoxyphthalides , 1990 .

[39]  B. Heil,et al.  Amines as ligands in transfer hydrogenation catalysts , 1989 .

[40]  R. Noyori,et al.  Homogeneous asymmetric hydrogenation of functionalized ketones , 1988 .

[41]  S. Heilmann,et al.  A new synthesis of 2-aminoalcohols from O-trimethylsilylated cyanohydrins , 1986 .

[42]  Manuel A Martínez,et al.  Rhodium(I) complexes in hydrogen transfer reactions to ketones and aldehydes , 1986 .

[43]  J. Saavedra.  Reductive alkylation of .beta.-alkanolamines with carbonyl compounds and sodium borohydride , 1985 .

[44]  G. Mestroni,et al.  [Ir(3,4,7,8-Me4phen) (CH2CH2)2Cl]: A very active catalyst precursor for hydrogen transfer from alcohols to unsaturated organic substrates , 1981 .

[45]  M. Queiros,et al.  Complexes of the platinum metals. 13. .beta.-Diketonato derivatives of ruthenium, osmium, and iridium , 1978 .

[46]  Anthony K. Smith,et al.  Arene ruthenium(II) complexes formed by dehydrogenation of cyclohexadienes with ruthenium(III) trichloride , 1974 .

[47]  F. Calderazzo,et al.  Reactions of some metal carbonyls with chelating compounds containing active protons, especially Schiff's bases , 1969 .

[48]  P. Jones,et al.  Ring-Chain Tautomerism in o-Acylbenzoic Acids. A Comparison of Experimental Methods and a Study of Substituent Effects1 , 1965 .