Keto esters, enantioselective hydrogenation

Collier P.J., Goulding T., Iggo J.A. and Whyman R. (1995) Studies of the Pt-cinchona alkaloid catalyst for enantioselective alpha-keto esters hydrogenation, in Jannes G. and Dubois V. (eds.). Chiral Reactions in Heterogeneous Catalysis, Plenum Press, N.Y. p. 105-110. 

The principles of the SE were applied for two enantioselective hydrogenation reactions (i) hydrogenation of P-keto esters over Ni-tartrate and (ii) hydrogenation of a-keto esters over cinchona-Pt/Al203 catalysts. In this respect the tartaric acid - P-keto ester system gave a negative result. Neither the substrate nor the modifier have bulky substituents required for SE. 

CDj a The simplified reaction scheme for the enantioselective hydrogenation of a-keto esters over cinchona-Pt/Al203 catalyst can be written as follows ... 

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. 

More recently, these authors have reported the synthesis of a new thiophene-based analogue of (I ,i )-Me-DuPHOS called UlluPHOS. The facial recognition and enantioselection associated with ruthenium complexes of UlluPHOS and Me-DuPHOS were shown to be similarly high in various hydrogenations of p-keto esters (Scheme 8.32). The most important difference between these two ligands was found by comparing the reaction rates. Indeed, the authors have observed that the use of UlluPHOS considerably increased the activity of the complexes. 

Table 24.3, Enantioselective hydrogenation of P-keto esters using Ru(II)-complexes.

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... 

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. 

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) -... 

Table28.8 Enantioselective hydrogenation of/l-keto esters using monodentate phosphine ligands.

Enantioselective Ketone and / -Keto Ester Hydrogenations (Including Mechanisms)... 

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