Asymmetric hydrogenation -2-acetamidocinnamate

Asymmetric synthesis is a method for direct synthesis of optically active amino acids and finding efficient catalysts is a great target for researchers. Many exceUent reviews have been pubHshed (72). Asymmetric syntheses are classified as either enantioselective or diastereoselective reactions. Asymmetric hydrogenation has been appHed for practical manufacturing of l-DOPA and t-phenylalanine, but conventional methods have not been exceeded because of the short life of catalysts. An example of an enantio selective reaction, asymmetric hydrogenation of a-acetamidoacryHc acid derivatives, eg, Z-2-acetamidocinnamic acid [55065-02-6] (6), is shown below and in Table 4 (73). 

Table 4. Asymmetric Hydrogenation of (Z)-2-Acetamidocinnamic Acid (6) to (f -At-Acetylphenylalanine (7)...

The influence of the concentration of hydrogen in [BMIM][PFg] and [BMIM][BF4] on the asymmetric hydrogenation of a-acetamidocinnamic acid catalyzed by rhodium complexes bearing a chiral ligand has been investigated. FFydrogen was found to be four times more soluble in the [BFJ -based salt than in the [PFg] -based one. 

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... 

A TYPICAL PROCEDURE FOR THE ASYMMETRIC HYDROGENATION OE METHYL (Z)-2-ACETAMIDOCINNAMATE... 

The new ligands were evaluated in the Rh-catalyzed asymmetric hydrogenation of benchmark substrates methyl a-N-acetamidoacrylate (7), methyl a-(2)-N-acetamidocinnamate (8) and dimethyl itaconate (9) (Table 2.3). For all three substrates, catalyst performance was superior in CH2CI2. Differences of up to 83% ee compared to otherwise identical reactions conducted in MeOH could be noted, giving... 

Recently, carbohydrate amphiphiles have been tested in the asymmetric hydrogenation of (Z)-methyl a-acetamidocinnamate in water (98). With a rhodium(I)-BPPM complex, 50% of the reactant was converted in 5 min, and enantioselectivities up to 96% were observed. A comparison of amphiphiles with alkyl chains of different lengths showed that micelle-forming properties, hydrophilic-lipophilic balance, and the structure caused by hydrogen bonding in the head group may be responsible for these effects. 

The insolubilized DIOP catalyst (34) was found to be rather ineffective for the asymmetric hydrogenation of oleflnic substrates the hydrogenation of a-ethyl-styrene proceeded readily but gave (-)-R-2-phenylbutane with an optical purity of only 1.5%. Methyl atropate was hydrogenated to (+)-S-methylhydratropate (2.5% ee). The soluble DIOP catalyst gave 15 and 17% ee, respectively, for the same reductions. The optical purity of the products was lower when recovered insolubilized catalyst was used. There was no reduction of a-acetamidocinnamic acid in ethanol-benzene with the insolubilized catalyst, presumably due to the hydrophobic nature of the polymer support causing it to shrink in hydroxylic solvents. 

Table 1. Asymmetric hydrogenation of o<-acetamidocinnamic acid catalyzed by palladiumfll) on polyfamino acid) (5-6)...

A number of groups have shown interest in the mechanism of asymmetric hydrogenation, principally of (a)-Z-acetamidocinnamic add and its derivatives. Kagan and co-workers have shown that cis addition of deuterium occurs to the Z isomer. Rhodium complexes of DIOP were used here. Koenig and Knowles obtained similar results with the ligands DIPAMP, cyclohexyl(o-... 

Later, Halpem conducted the same experiments using a Rh-DIPAMP complex to catalyze hydrogenation of methyl-(Z)-l-acetamidocinnamate (MAC), and the results were entirely analogous to the CHIRAPHOS system.11 The important lesson learned in Section 9-4-2 again applies in the mechanism for asymmetric hydrogenation—isolable intermediates such as 7 are typically not the active species involved in a catalytic cycle.12... 

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