Ruthenium catalysts keto ester asymmetric hydrogenation

Asymmetric hydrogenation has been achieved with dissolved Wilkinson type catalysts (A. J. Birch, 1976 D. Valentine, Jr., 1978 H.B. Kagan, 1978). The (R)- and (S)-[l,l -binaph-thalene]-2,2 -diylblsCdiphenylphosphine] (= binap ) complexes of ruthenium (A. Miyashita, 1980) and rhodium (A. Miyashita, 1984 R. Noyori, 1987) have been prepared as pure atrop-isomers and used for the stereoselective Noyori hydrogenation of a-(acylamino) acrylic acids and, more significantly, -keto carboxylic esters. In the latter reaction enantiomeric excesses of more than 99% are often achieved (see also M. Nakatsuka, 1990, p. 5586). 

Enantioselectivities in the range of 97.7-99.9%, with the majority in the range of 98.4-99.1%, are obtained in the asymmetric hydrogenation of aryl alkyl ketones with ruthenium catalyst 109.641 The same systems can hydrogenate /3-keto esters (95.2-98.6% ee) and a,/i-unsa(urated acids (96.2% in a single example).642... 

This ligand, MeO-BIPHEP (96a), has shown similar reactivities and enantioselectivities to catalysts that contain BINAP.117 Ruthenium catalysts that contain MeO-BIPHEP have been used in several asymmetric hydrogenations from bench scale to multi-ton scale, which include the large-scale preparation of a P-keto ester, an aryl ketone, allylic alcohol, and several oc,P-unsaturated carboxylic acid substrates, which are shown in Figure 12.5. 

Ruthenium catalysts that contain Cl-MeO-BIPHEMP have been used in the asymmetric hydrogenation of P-keto esters (99% ee)126 and the dynamic kinetic resolution of substituted P-keto esters (Scheme 12.33).121 The asymmetric hydrogenation of methyl 3,3-dimethyl-2-oxobutyrate to the corresponding a-hydroxy ester has been reported with ruthenium catalyst, RuBr2[(-)-Cl-MeO-BIPHEMP] 2 (Scheme 12.34).121... 

Rhodium and ruthenium complexes of CHIRAPHOS are also useful for the asymmetric hydrogenation of p-keto esters. Dynamic kinetic resolution of racemic 2-acylamino-3-oxobutyrates was performed by hydrogenation using ((5,5)-CHIRAPHOS)RuBr2 (eq 3). The product yields and enantiomeric excesses were dependent upon solvent, ligand, and the ratio of substrate to catalyst. Under optimum conditions a 97 3 mixture of syn and anti p-hydroxy esters was formed, which was converted to o-threonine (85% ee) and D-allothreonine (99% ee) by hydrolysis and reaction with propylene oxide. 

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. 

Another ruthenium catalyst, such as an Ru(t/ -arene)-A-perfluorosulfonyl-l, 2-diamine, was applied to the asymmetric transfer hydrogenation of jS-keto-a-methylamino acid esters, affording /l-(3,4-dimethoxyphenyl)serine methyl esters as shown in Scheme 2.11 °... 

Very recently. Steward and Johnson developed the DKR of jS-silyloxy-a-keto esters, previously prepared through a cyanide-catalysed benzoin-type reaction between silyl glyoxylates and aldehydes. The asymmetric transfer hydrogenation was performed in the presence of TEA as the base, formic acid as the hydride source, and a ruthenium catalyst bearing a chiral 1,2-diamine, providing the corresponding enantioenriched monoprotected diols with moderate diastereo- and enantioselectivities of up to 66% de and 52% ee, respectively. 

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