Acetamidoacrylic acid

Another important example of an enantioselective reaction mediated by a chiral catalyst is the hydrogenation of 3-substituted 2-acetamidoacrylic acid derivatives. 

Scheme 2.12. Enantioselective Reduction of 2-Acetamidoacrylic Acids by Chiral Phosphine Complexes of Rhodium...

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.

Wan and Davis135,138 modified rhodium complexes with the water soluble chiral tetrasulfonated binap ligand 26 (Table 2) and used them as catalysts in the asymmetric hydrogenation of 2-acetamidoacrylic acid in aqueous media. The e.e. observed in neat water using Rh/26 was approximately the same as that obtained with the unsulfonated Rh/binap in ethanol (68-70% versus 67%).135... 

Itaconic acid (Eastman) and 2-acetamidoacrylic acid (Fluka) were CP grade a tropic acid was prepared according to the literature (53). Ruthenium and rhodium trichlorides were obtained as trihydrates from Johnson Matthey Limited. (+)Diop was obtained from Strem Chemicals a literature synthesis provided (-)diop (7). Racemic methyl phenyl sulfoxide was a K K product. 

In addition to the high enantioselectivity, the rate of the hydrogenation using Rh(7 -SpirOP) catalyst is also very fast. When a substrate/catalyst ratio of 10000 was used and when the reaction was carried out at ambient temperature under 200 psi H2, >99.9% conversion of 2-acetamidoacrylic acid to 2-acetamidopropionic acid (96.8% ee) was observed in 1 h. The detailed results are shown in Table 3. 

Table 3 The Rh(l -SpirOP) -catalyzed asymmetric hydrogenation of 2-acetamidoacrylic acid with different S/C ratio ...

Figure 3. Rhodium-catalyzed hydrogenation of 2-acetamidoacrylic acid with a BPPM-type phosphine on an optically active support.

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. 

Enantioselective reduction of 2-acetamidoacrylic acids by chiral phosphine complexes of rhodium... 

Acetamidoacrylic acid and other unsaturated acids 2-Acetamidoacrylic acid and other unsaturated acids PhCHC(NHAc)COOH... 

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