Ketones ruthenium hydrogenation

Palmer and Wills in 1999 reviewed other ruthenium catalysts for the asymmetric transfer hydrogenation of ketones and imines [101]. Gladiali and Mestro-ni reviewed the use of such catalysts in organic synthesis up to 1998 [102]. Review articles that include the use of ruthenium asymmetric hydrogenation catalysts cover the literature from 1981 to 1994 [103, 104], the major contributions... 

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... 

Great care must be taken not to generalize these effects, as the addition of primary diamines to ruthenium bisphosphine complexes generates a very active catalyst for ketone hydrogenation after the addition of base (see Chapter 32). 

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. 

Catalysts for ketone hydrogenation continue to be developed but one of the best systems is still the BINAP-DPEN catalyst first reported by Ohkuma et al. in 1995. " In this system ruthenium is combined with both a chiral diphosphine and a chiral diamine, forming an octahedral complex which gives a high degree of enantioselectivity. This stereoselectivity is considered to be a result of the synergistic effect of the chiral diphosphine and diamine ligands. 

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

A benzophenone-based ruthenium complex (15) afforded high enantioselectivity in the catalytic asymmetric ketone hydrogenation (up to 99% ee, >99% yield). It was found that chirality of benzophenone complexes can be controlled even in the solution phase.332... 

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... 

Scheme 7 Reaction of ruthenium hydrido-amido complex 11 with hydrogen to give the dihydride 12 during ketone hydrogenation...

Unlike most rhodium homogeneous catalysts, the ruthenium(BlNAP) series is very effective for the asymmetric hydrogenation of functional ketones48. This leads to a number of experimental circumstances where the directing effect of substituents is brought into play. One of the most commonly used examples of asymmetric ketone hydrogenation is that of /1-keto esters. Diketone reduction with ruthenium[(5)-BINAP] demonstrates the high enantiomeric purity due to double asymmetric induction. 

The sertraline precursor is a chiral alcohol with the stereogenic centre adjacent to an aromatic ring. An obvious approach is to make the hydroxyl group by asymmetric reduction of the corresponding ketone. CBS reduction is a possibility, as is a ruthenium-catalysed hydrogenation using the ligand TsDPEN (p. 1115 of the textbook). 

Ruthenium and rhodium complexes have maintained the best track record as ketone hydrogenation catalysts. For high enantioselectivities, additional chelating functional groups are often needed. Typical substrates are represented by ketones (3.01) to (3.03), where esters, halides and phosphonates provide an additional donor group on the substrate. BlNAP/ruthenium combinations, such as complex (3.07), have given consistently high enantioselectivities with such... 

The hydrogenation of unfunctionalised ketones has, in the past, proved challenging. However, Noyori and coworkers have discovered that the activity of ruthenium-based ketone hydrogenation catalysts can be greatly improved on incorporation of... 

Interactive mechanism for ruthenium-catalysed ketone hydrogenation... 

More polar functional groups such as ketones are hydrogenated effectively with homogeneous cationic rhodium and ruthenium complexes. Polymer catalysts active for both olefin and ketone hydrogenation activity were synthesized from ionic precursors such as Rh(norbornadiene)(acac) + HCIO4 or Rh(norbornadiene)(PE 3)2 + C104. Two types of coordination were observed, depending on the method of attachment " ... 

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... 

Itsuno et al. [21] synthesized a cross-linked polymer support with a chiral 1,2-diamine for enantioselective ruthenium transfer hydrogenation catalysis of aromatic ketones. 

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. 

The application of dynamic kinetic discrimination to the ruthenium-catalysed hydrogenation of cyclic ketones such as 2-arylated cycloalkanones was reported by Noyori s group in 2004. Hence, the asymmetric hydrogenation of various 2-arylcycloalkanones with tra s -RuCl2(BINAP)(l, 2-diamine) and t-BuOK in ijo-propyl alcohol selectively gave the corresponding cis-2-arylcycloalkanols in excellent enantiomeric purity and quantitative yield, as shown in Scheme 2.25. 

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