Asymmetric hydrogenation optical yields

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. 

However, the optical yield of the product for asymmetric hydrogenation in an aqueous medium is generally lower than those obtained... 

The bis-DIOP complex HRh[(+)-DIOP]2 has been used under mild conditions for catalytic asymmetric hydrogenation of several prochiral olefinic carboxylic acids (273-275). Optical yields for reduction of N-acetamidoacrylic acid (56% ee) and atropic acid (37% ee) are much lower than those obtained using the mono-DIOP catalysts (10, II, 225). The rates in the bis-DIOP systems, however, are much slower, and the hydrogenations are complicated by slow formation of the cationic complex Rh(DIOP)2+ (271, 273, 274) through reaction of the starting hydride with protons from the substrate under H2 the cationic dihydride is maintained [cf. Eq. (25)] ... 

A chiral catalyst consisting of Irans-RuC]2(xy]binap)(daipen) and (CH3)3COK in 2-propanol effects asymmetric hydrogenation of a-, / -, and y-amino aromatic ketones [128]. Hydrogenation of 2-(dimethylamino)acetophenone catalyzed by the (R)-XylBINAP/(R)-DAIPEN-Ru complex [(R,R)-31D] gives the R amino alcohol in 93% ee (Fig. 32.36). The optical yield is increased up to 99.8%, when... 

When the C=N bond is fixed in a ring system in which no (E)/(Z) isomerization can take place, the asymmetric hydrogenation of the C=N bond can be highly enantioselective. Oppolzer et al." found that cyclic sulfonimide was hydrogenated with an Ru(BINAP) catalyst to give a product with essentially quantitative optical yield (Scheme 6-45). 

A classical example is the development of soluble chiral catalysts for homogenous asymmetric hydrogenation. The story began with the discovery of Wilkinson s catalyst [4]. In 1968, Horner [5] and Knowles [6], independently, reported the feasibility of asymmetric hydrogenations in the presence of optically active Wilkinson-type catalyst. Although the optical yields were rather low, further studies in this direction were the basis of the success of Monsanto s asymmetric synthesis of the anti-Parkinson s drug L-DOPA. The key steps of the synthesis are outlined in Scheme 11.1. 

Figure 1.25 exemplifies the strucmres of certain efficient precatalysts for asymmetric transfer hydrogenation of ketones. Precatalysts C1-C3 use the NH effect described above. A turnover frequency, defined as moles of product per mol of catalyst per hour, of 30,000 h is achieved by using of C2 and an alkaline base in 2-propanol. A Rh complex C3 is an isolobal to the corresponding arene-Ru complex (see Figure 1.23). The Ru complexes C4 " and C5 without NH group in ligand catalyze the reaction by different mechanisms. A higher than 90% optical yield is achieved by using C5 in reduction of certain aliphatic ketones.

Asymmetric Hydrogenation. Asymmetric hydrogenation with good enantio-selectivity of unfunctionalized prochiral alkenes is difficult to achieve.144 145 Chiral rhodium complexes, which are excellent catalysts in the hydrogenation of activated multiple bonds (first, in the synthesis of a-amino acids by the reduction of ol-N-acylamino-a-acrylic acids), give products only with low optical yields.144 146-149 The best results ( 60% ee) were achieved in the reduction of a-ethylstyrene by a rhodium catalyst with a diphosphinite ligand.150 Metallocene complexes of titanium,151-155 zirconium,155-157 and lanthanides158 were used in recent studies to reduce the disubstituted C—C double bond with medium enantioselectivity. 

Reaction Conditions versus Selectivity. [Rh(binap)(CH30H)2]C104 is an excellent chiral catalyst for asymmetric hydrogenation (13, 16). Scheme 5 relates the double bond geometry of the starting materials, the configuration of the BINAP ligand, and the stereochemistry of the products. The optical yield and the sense of asymmetric induction are... 

With DIOP-Pd(0) or -Ni(0) complexes as catalysts, moderate optical yields of up to 35% have been observed (126). Norbomene is convertible to the exo nitrile with up to 40% ee when a BINAP-Pd(0) complex is used (Scheme 57) (127). Ni(0) complexes of sugar-derived 1,2-diol phosphinites catalyze highly selective asymmetric addition of hydrogen cyanide to vinylarenes (128). This method gives the 2-naphthalene-2-propionitrile precursors of nonsteroid anti-inflammatory agents in up to 85% ee and in high yield. 

Another useful method is the modification of Pt black by cinchona alkaloids, initially developed by Orito, which permits the asymmetric hydrogenation of a-keto esters in up to 90% optical yield (Scheme 17) (43). The reaction with Pt-Al203 modified by cinchonidine can be carried out on 10-200-kg scale in greater than 98% chemical yield and in... 

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