Ruthenium-catalyzed hydrogenation ketones

Increasing effort has been applied to develope asymmetric transfer hydrogenations for reducing ketones to alcohols because the reaction is simple to perform and does not require the use of reactive metal hydrides or hydrogen. Ruthenium-catalyzed hydrogen transfer from 2-propanol to ketones is an efficient method for the preparation of secondary alcohols. 

C3-TunePhos (1,13-bis(diphcnylphosphino)-7,8-dihydro-6//-dibenzo f,h] [l,5]dioxonin) ruthenium catalyzes the hydrogenation of a-phthalimido ketones with enantioselectivities of >94%,651 leading to a highly enantioselective route to /3-aminoethanols. 

Trost et al 2 briefly explored using non-enone enophiles. Simple alkenes led to the formation of complex mixtures of isomers due to the presence of an additional set of /3-hydrogens. Many other types of substrates were incompatible with reaction conditions. Vinyl ketones were, therefore, the only coupling partners shown to be effective in the ruthenium-catalyzed Alder-ene couplings of allenes and alkenes. 

Recently, the first report was made on the ruthenium-catalyzed enantioselective hydrogenation of aryl-methyl ketones using monodentate phosphonites (Scheme 28.18). In particular, ligand 15f induced excellent ee-values. One very early report on rhodium-catalyzed hydrogenation of ketones using the monophosphine bmpp 1 f met with a low e.e. [95]. 

The enantioseiective hydrogenation of a-amino ketones has been applied extensively to the synthesis of chiral drugs such as the / -agonist SR 58611 (Sanofi Cie). m-Chlorstyreneoxide was obtained via carbene-induced ring closure of the amino alcohol. Epoxide-opening by a chiral amine obtained via a ruthenium-catalyzed hydrogenation of an enamide has led to the desired compound where... 

A. Ruthenium Catalyzed Asymmetric Transfer Hydrogenation (ATH) TO Ketones... 

Ruthenium-Catalyzed Asymmetric Hydrogenation of Aromatic Ketones... 

A -ARENESULFONYL- AND A-ALKYLSULFAMOYL-1,2-DIPHENYLETHYLENEDIAMINE LIGANDS FOR RUTHENIUM-CATALYZED ASYMMETRIC TRANSFER HYDROGENATION OF ACTIVATED KETONES... 

SYNPHOS AND DIFLUORPHOS AS LIGANDS FOR RUTHENIUM-CATALYZED HYDROGENATION OF ALKENES AND KETONES... 

K. Evetraere, J.-F. Carpentier, A. Morteux, and M. Bulliard, N-Benzoyl-norephedrine derivatives as new, effident ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of functionalized ketones, Tetrahedron Asymm. 1999, 10, 4083 4086. 

The asymmetric hydrogenation of enol esters is an alternative to asymmetric ketone hydrogenation. The precursors can be prepared from the ketones but also via ruthenium-catalyzed addition of the carboxylic acids to the 2-postion of terminal alkynes. This latter method allows the study of the effect of the carboxylate on the enantioselectivity of the asymmetric hydrogenation. A remarkable study by Reetz and colleagues established that it is possible to hydrogenate enolate... 

The number of publications describing new ligands that allow the transfer hydrogenation of aromatic ketones with over 90 % ee has grown in leaps and bounds since 1996 [15]. In these reactions the use of ruthenium [15a-f] and iridium [15g] as the catalytically active metals has recently been augmented by the use of phosphorus-free ligands such as chiral diamines, amino alcohols, and bisthioureas such as 7 [15a,e-g]. A ruthenium-catalyzed transfer hydrogenation with 92 % ee has even been reported for the aliphatic ketone pinacolone (tert-butyl methyl ketone) [16]. 

Having demonstrated the potential of artificial metalloenzymes for the reduction of V-protected dehydroaminoacids, we turned our attention towards organometallic-catalyzed reactions where the enantiodiscrimination step occurs without coordination of one of the reactants to the metal centre. We anticipated that incorporation of the metal complex within a protein enviromnent may steer the enantioselection without requiring transient coordination to the metal. In this context, we selected the palladium-catalyzed asymmetric allylic alkylation, the ruthenium-catalyzed transfer hydrogenation as well as the vanadyl-catalyzed sulfoxidation reaction. Indeed, these reactions are believed to proceed without prior coordination of the soft nucleophile, the prochiral ketone or the prochiral sulfide respectively. Figure 13.5. 

Three pathways for the ruthenium-catalyzed hydrogenations of ketones, aldehydes, and a,(3-unsaturated aldehydes with several catalyst systems were studied the direct insertion, the migratory insertion, and the concerted hydrogen transfer highlighting the catalyst/substrate configurations that lead to stereoselective differentiation. The contribution of computational chemistry were essential to differentiate these mechanisms of ruthenium-catalyzed reactions and to rationalize the experimentally observed stereochemical outcome. 

Chemoselective Ruthenium-Catalyzed Hydrogenation of Ketones and Aldehydes. 53... 

The selective domino dienyne metathesis of 94 with Grubbs catalyst 2 to give the fused 5/9-bicyclic substructure embedded in 95 controlled by olefin substitution was coupled in a sequential manner with a chemoselective ruthenium-catalyzed hydrogenation of the disubstituted alkene of 95 to yield the tricyclic protected amino ketone 96 in a one-pot process (Scheme 2.35) [18h]. Only two further steps were required to convert 96 into the Lycopodium alkaloid (+)-lycoflexine. 

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