Hydrogenation methyl acetamidoacrylic acid

The ligand prepared as indicated was used to prepare the rhodium complex [Rh (/J)-BINAP(S03Na)4 (H20)2] , which hydrogenates 2-acetamidoacrylic acid and its methyl ester with the same enantiomeric efficiency as the traditional catalyst in a nonaqueous solvent. A subsequent study (Wan and Davis, 1993b) showed that a ruthenium-sulfonated-BINAP complex can also be an effective hydrogenation catalyst in both methanolic and neat water solvent systems. 

The preparation of this type of catalyst is quite simple. HPAs such as phos-photungstic acid were adsorbed onto inorganic supports such as clays, alumina, and active carbon. Subsequently, the metal complex was added to form the immobilized catalyst. If necessary, the catalyst can be pre-reduced. These types of catalysts were developed mainly for enantioselective hydrogenations. For instance, a supported chiral catalyst that was based on a cationic Rh(DIPAMP) complex, phosphotungstic acid and alumina showed an ee-value of 93% with a TOF of about 100 IT1 in the hydrogenation of 2-acetamidoacrylic acid methyl ester (Fig. 42.4 Table 42.2). 

Fig. 42.4 Enantioselective hydrogenation of 2-acetamidoacrylic acid methyl ester.

The most commonly employed substrates are (Z)-a-acetamidocinnamic acid (ACA), its methyl ester (MAC), acetamidoacrylic acid (AAA) and its methyl ester (MAA). Quantitative yields at mild hydrogen pressure (1-3 atm) are usually obtained with these substrates. Values of ee very close to 100% have been reached for dozens ligands, including many P-stereogenic phosphines. The most successful examples of the hydrogenation of a-dehydroamino acid derivatives are listed in Table 7.1. 

The hydrogenation of jS-acetamidoacrylates has also been achieved under similar conditions to give /3-amino-acid derivatives of ca. 55% optical purity. An example of chiral induction at two adjacent carbon atoms is the hydrogenation of dimethyl (Z)-2-acetamido-3-methylfumarate, in the presence of a chiral cationic pyrrolidine-phosphine Rh complex, which leads to (2R,3R)-/3-methyl-aspartic acid of about 55% enantiomeric enrichment. Studies of the mode of action of the aforementioned catalyst have been carried out and a flexible synthesis of functionalized chelating diphosphines has been described. ... 

In asymmetric hydrogenation of olefins, the overwhelming majority of the papers and patents deal with hydrogenation of enamides or other appropriately substituted prochiral olefins. The reason is very simple hydrogenation of olefins with no coordination ability other than provided by the C=C double bond, usually gives racemic products. This is a common observation both in non-aqueous and aqueous systems. The most frequently used substrates are shown in Scheme 3.6. These are the same compounds which are used for similar studies in organic solvents salts and esters of Z-a-acetamido-cinnamic, a-acetamidoacrylic and itaconic (methylenesuccinic) acids, and related prochiral substrates. The free acids and the methyl esters usually show appreciable solubility in water only at higher temperatures, while in most cases the alkali metal salts are well soluble. 

As enantioselective hydrogenations of prochiral substrates are undoubtedly the most common applications of chiral diphosphine ligands, a broad screening of our ligands was undertaken with some commonly used standard substrates. As substrates for the hydrogenation of C=C double bonds dimethyl itaconate (DlMl), methyl 2-acetamidoacrylate (MAA), methyl acetamidocinnamate (MAC) as an a-amino acid precursor, and ethyl (Z)-3-acetamidobutenoate ( 3-ENAM1DE) as a p-amino acid precursor were chosen (see Eig. 1.4.5). 

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