Keto esters, asymmetric

Keto Esters Asymmetric transfer hydrogenation of functionalized ketones is rare. However, an excellent optical yield is obtainable inreduction of methyl benzoylformate by using 2-propanol and with a catalyst system consisting of [RhCl(C6H]0)]2, (S,S)-DMDPEN, and KOH (Scheme 1.89) [313],... 

Rhodium and palladium catalysts that contain 4 display high enantioselectivities for the asymmetric hydrogenation of enamides, itaconates, P-keto esters, asymmetric hydroboration, and asymmetric allylic alkylation,80 82 but this ligand system distinguishes itself from other chiral bisphos-phines in the asymmetric reduction of tetrahydropyrazines and tetrasubstituted olefins (see also Chapter 15). The reduction of tetrahydropyrazines produces the piperazine-2-carboxylate core,... 

The asymmetric Henry reaction is important because products are convertible to many other valuable bifunctional or polyfunctional compounds. Organocatalysts for the reaction containing a guanidine unit are represented by the C2-symmetric 76, which directs the addition of nitroalkanes to a-keto esters asymmetrically. 

Dynamic kinetic resolution of racemic ketones proceeds through asymmetric reduction when the substrate does racemize and the product does not under the applied experimental conditions. Dynamic kinetic resolution of a-alkyl P-keto ester has been performed through enzymatic reduction. One isomer, out of the four possible products for the unselective reduction (Figure 8.38), can be selectively synthesized using biocatalyst, and by changing the biocatalyst or conditions, all of the isomers can be selectively synthesized [29]. 

Scheme 28. Examples of Ru-catalyzed asymmetric hydrogenation reactions of /i-keto esters...

Catalytic asymmetric hydrogenation is a relatively developed process compared to other asymmetric processes practised today. Efforts in this direction have already been made. The first report in this respect is the use of Pd on natural silk for hydrogenating oximes and oxazolones with optical yields of about 36%. Izumi and Sachtler have shown that a Ni catalyst modified with (i ,.R)-tartaric acid can be used for the hydrogenation of methylacetoacetate to methyl-3-hydroxybutyrate. The group of Orito in Japan (1979) and Blaser and co-workers at Ciba-Geigy (1988) have reported the use of a cinchona alkaloid modified Pt/AlaO.i catalyst for the enantioselective hydrogenation of a-keto-esters such as methylpyruvate and ethylpyruvate to optically active (/f)-methylacetate and (7 )-ethylacetate. 

Roche carries out asymmetric hydrogenation of a p-keto-ester for a pancreatic lipase inhibitor using their Ru (II) BIHEHP catalyst. For scaling up, Roche decided to use a heterogeneous catalyst, modified Ni /L-tartaric acid with NaBr, since this was economically more attractive. 

McKervey and Ye have developed chiral sulfur-containing dirhodium car-boxylates that have been subsequently employed as catalysts for asymmetric intramolecular C-H insertion reactions of y-alkoxy-ot-diazo-p-keto esters. These reactions produced the corresponding ci -2,5-disubstituted-3(2H)-furanones with diastereoselectivities of up to 47% de. Moreover, when a chiral y-alkoxy-a-diazo-p-keto ester containing the menthyl group as a chiral auxiliary was combined with rhodium(II) benzenesulfoneprolinate catalyst, a considerable diastereoselectivity enhancement was achieved with the de value being more than 60% (Scheme 10.74). 

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... 

The TunaPhos ligands of general structure 114, when complexed with [RuPhCl2]2, bring about the asymmetric hydrogenation of /1-keto esters with... 

In the early 1990s, Burk introduced a new series of efficient chiral bisphospholane ligands BPE and DuPhos.55,55a-55c The invention of these ligands has expanded the scope of substrates in Rh-catalyzed enantioselective hydrogenation. For example, with Rh-DuPhos or Rh-BPE as catalysts, extremely high efficiencies have been observed in the asymmetric hydrogenation of a-(acylamino)acrylic acids, enamides, enol acetates, /3-keto esters, unsaturated carboxylic acids, and itaconic acids. 

Table 10 Asymmetric hydrogenation of some a-keto esters or amides...

Yang12 has effected an intramolecular asymmetric carbonyl-ene reaction between an alkene and an a-keto ester. Reaction optimization studies were performed by changing the Lewis acid, solvent, and chiral ligand. Ligand-accelerated catalysis was observed for Sc(OTf)3, Cu(OTf)2, and Zn(OTf)2 (Equation (6)). The resulting optically active m-l-hydroxyl-2-allyl esters provide an entry into multiple natural products. 

The hydrogenation of ketones with O or N functions in the a- or / -position is accomplished by several rhodium compounds [46 a, b, e, g, i, j, m, 56], Many of these examples have been applied in the synthesis of biologically active chiral products [59]. One of the first examples was the asymmetric synthesis of pantothenic acid, a member of the B complex vitamins and an important constituent of coenzyme A. Ojima et al. first described this synthesis in 1978, the most significant step being the enantioselective reduction of a cyclic a-keto ester, dihydro-4,4-dimethyl-2,3-furandione, to D-(-)-pantoyl lactone. A rhodium complex derived from [RhCl(COD)]2 and the chiral pyrrolidino diphosphine, (2S,4S)-N-tert-butoxy-carbonyl-4-diphenylphosphino-2-diphenylphosphinomethyl-pyrrolidine ((S, S) -... 

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