Methyl acetoacetate hydrogenation

Table 41.18 Homogeneous, biphasic and heterogeneous enantioselective hydrogenations of methyl acetoacetate with Ru-BINAP [117],...

To our knowledge, there is to date only one report concerning asymmetric hydrogenation using a SILP catalyst [117]. Methyl acetoacetate was hydrogenated using Ru-BINAP dissolved in [BMIM][PF6] and immobilized on the poly(diallyl-dimethy-lammonium chloride) support (Fig. 41.14). 

Sodium methoxide, 3-methyl-4-nitroanisole, diethyl oxalate, 30% hydrogen peroxide, 97% sodium hydride, methyl acetoacetate, sodium sulfate, 10% palladium on activated carbon, ammonium formate, and 2-nitrophenylacetic acid were purchased from Aldrich Chemical Company, Inc., and were used without further purification. 

Hydrogenation of methyl acetoacetate was successfully carried out in water catalyzed by a complex obtained in situ from [ RuCl2(benzene)2 2] + (/ 9-(+)BIFAPS (50) (Scheme 3.22). Spectacular effects of small amounts of added HCl or H2SO4 were found under comparable conditions the conversion increased from 58% to 100% and the e.e. from 22% to 86% [111]. The origin of this effect of acids is unclear it was speculated that... 

Ligand (349), water-soluble (350), and their (R)-enantiomers have been synthesized, and their Ru complexes used as catalysts (see also Section 5.5.3.2.5) for the asymmetric hydrogenation of methyl acetoacetate and (Z)-acetamidocinnamic acid. " The complex [Ru (5)-351 (OAc)2] and... 

For instance, RNi modified with an optically active amino acid or hydroxy acid hydrogenates methyl acetoacetate (MAA) to produce optically active methyl 3-hydroxybutyrate (MHB) as shown in Fig. 1. 

Random screening is usually too time consuming but a certain randomness is desirable during the exploratory phase because unexpected effects are bound to occur. Again a citation Tai [1] says regarding the discovery of the Ni/tartrate/NaBr catalyst and its application to p-keto ester hydrogenation "It was sheer luck that methyl acetoacetate was employed as a substrate...". 

Fig. 8. Effect of the modifier structure on the optical yield for the hydrogenation of methyl acetoacetate [4] and ethyl pyruvate [58],...

Kinetic studies and mechanistic schemes. With this paragraph we will conclude our survey on the mechanism of chirally modified hydrogenation catalysts. Several kinetic studies have been carried out using various Ni catalysts both in the liquid and the gas phase [1,4, 55]. Activation energies were found to be 10-15 kcal/mol. The reaction was first order in catalyst. Reaction orders for H2 ranged from 0 to 0.2 in the gas phase and from 0 to 1 in liquid phase while for methyl acetoacetate values of 0.4-1 (gas phase) and 0.2-0.8 (liquid phase) were determined. Based on these findings and on many other observations two mechanistic schemes were proposed ... 

Comparisons in the asymmetric hydrogenation of methyl acetoacetate (111) with ruthenium catalysts that contain C2-Tunephos (110b) and 116 indicated an improvement in enantiomeric excess when the ether linkage contained additional chirality.134140... 

Later, the optical yields over the modified Raney Ni were greatly improved by hydrogenating the substrate in the presence of sodium bromide.210 Thus, the best optical yield of 88.6% ee was obtained in the hydrogenation of methyl acetoacetate over Raney Ni modified 3 times with tartaric acid in the presence of sodium bromide with addition of a small amount of acetic acid (eq. 5.48). 

A more specific interaction between a zeolite surface and a chiral catalyst was recently uncovered (58). It was found that the Ru-binap catalyst can be specifically withheld on the outer surface of Beta zeolites. Such a heterogeneous catalyst is relevant for the highly enantioselective hydrogenation of methyl acetoacetate to (R) or (S) 3-hydroxymethylbutyrate, with typical ee values of about 95 %. 

Asymmetric hydrogenation. Raney nickel that has been soaked at 100° in an aqueous solution of tartaric acid and sodium bromide can effect asymmetric hydrogenation of methyl acetoacetate to methyl 3-hydroxybutyrate and of acetylacetone to 2,4-pentanediol/ In both cases optical yields near 90% can be achieved. 

Table 4 Hydrogenation of Methyl Acetoacetate over Raney Nickel Modified with Tartaric Acid-Inorganic Salt...

Although palladium on polypeptide sterns mentioned above are heterogei mis, homogeneous system may be realized by the complexation of ruthenium(III) ion to poly(S-glutamic acid), which was fwnd effective as catafyst for the asymmetric hydrogenation of methyl acetoacetate (Hirai, Aikawa, Fumta (7)). 

In connection with these studies, the a nunetric hydrogaiatkm catalyzed by Raney nickel modified with dipeptide ould be mentioned. In the hydrogenation of methyl acetoacetate [Eq. (5)], Izumi and his co-workers (JO) found that the... 

Keane MA, Webb G (1992) The enantioselective hydrogenation of methyl acetoacetate over supported nickel catalysts I. The modification procedure. 1 Catal 136 1 Keane MA (1997) Interaction of optically active tartaric acid with a nickel-sUica catalyst role of both the modification and reaction in determining enantioselectivity. Langmuir 13 41... 

Scheme 5.6 Hydrogenation of methyl acetoacetate (S) enantiomers of 21-23 were also tested.

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