Hydrogenation of keto esters

The enantioselective hydrogenation of /(-keto esters is important, because the resulting optically active /(-hydroxy esters are converted to useful chiral building blocks [1-4]. The development of BINAP-Ru(II) catalysts allowed the highly enantioselective hydrogenation of /(-keto esters. As shown in Figure 32.6, methyl-... 

Fig. 32.7 (R)-BINAP-Ru-catalyzed hydrogenation of/ -keto esters. (a) Catalytic cycle, (b) Transition-state models.

Highly enantioselective hydrogenation of / -keto esters is achieved by using a Raney Ni catalyst modified by tartaric add and NaBr (Fig. 32.14) [9, 55]. The catalyst should be prepared under controlled conditions induding suitable pH (3-4), temperature (100°C), and concentration of the modifier (1%) to achieve an optimum stereoselectivity. The addition of NaBr, an achiral modifier, is important. Furthermore, ultrasonic irradiation of the catalyst tends to increase the activity and enantioselectivity [9f,g]. Ultrasonication may remove nonselective sites of the catalyst surface. 

The same catalyst was used in the asymmetric hydrogenation of / -keto esters in [BMIM][PF6], [BMIM][BF4] and [MMPIM][(CF3S02)2N] with complete conversions and ee-values of up to 99.3% [108]. 

Table 9.2 Asymmetric hydrogenation of keto esters with BisP -Ru(II) catalysts.

The Ni-tartaric acid system was discovered by Izumi et al. [40] and gives, under optimized conditions, e.e.s >90% in the hydrogenation of -keto esters. Even with simple ketones good results are obtained, e.g., 2-octanone 80% e.e. [41]. As yet the mechanism of the enantioselectivity is not well understood. 

Figure 1.16. Chiral ligands useful for hydrogenation of keto esters.

Hydrogenation of / -keto ester with Ru-tmbtp multi 100 kg Chemi [20]... 

Route C Synthesis and Enantioselective Hydrogenation of Keto Ester 5... 

An improvement in the stereoselectivity is achieved by the use of nonfermenting yeast89. Although a very efficient method for catalytic asymmetric hydrogenation of / -keto esters has been reported154, baker s yeast reduction is still preferred155. 

Okamoto, S., Harada, T., and Tai, A. (1979) Enantioface-differentiating asymmetric hydrogenation of keto ester with modified nickel, XXXII., Structural requirements of modifying reagent and substrate. Bull. Chem. Soc. Jpn. 52, 2670 - 2673. 

Tanabe, T., and Izumi, Y. (1973) Asymmetric) hydrogenation of the C=0 double bond with modified Raney nickel, XXVI. Asymmetric hydrogenation of keto esters, Bw//. Chem. Soc. Jpn. 46, 1550-1551. 

In different ways solvents influence enantioselective hydrogenation of keto esters on chiral modified Pt-supported catalysts. The effect of solvent on enantioselective hydrogenation involves the solubility of hydrogen, the solubility of the reactant, and the interaction between modifier, reactant, and catalyst surface including the carrier (Singh et al. There are no general... 

LeBlond et al. applied unprecedented mild conditions for the enantioselective hydrogenation of keto esters, 5.8 bar instead of the commonly used 100 bar, over 1% Pt-alumina catalyst with 25% Pt dispersion, modified with DHCnd. In their standard experiment 1.4 g of 1% Pt-alumina, 400 ml AcOH, and 0.1 mol of EtPy were evacuated and stirred before applying hydrogen. 

Asymmetric Hydrogenation of Keto Esters in the Total Synthesis Statins ° are effective inhibitors of 3-... 

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