Asymmetric hydrogenation 2-arylacrylic acid

Asymmetric catalytic hydrogenation is one of the most efficient and convenient methods for preparing a wide range of enantiomerically pure compounds, and Ru-BINAP-catalyzed asymmetric hydrogenation of 2-arylacrylic acids has attracted a great deal of attention,11 as the chiral 2-arylpropionic acid products constitute an important class of nonsteroidal antiinflammatory drugs. 

Asymmetric Catalytic Hydrogenation of 2-Arylacrylic Acids as a Low-Cost Route to Pharmaceutical Products... 

The homogeneous catalytic asymmetric hydrogenations of 2-arylacrylic acids have been studied. Both rhodium and ruthenium catalysts have been examined. The reaction temperatures and hydrogen pressures have profound effects on the optical yields of the the products. The presence of a tertiary amine such as triethylamine also significantly increases the product enantiomer excess. Commercially feasible processes for the production of naproxen and S-ibuprofen have been developed based on these reactions. 

Although the Rh-catalyzed asymmetric hydrogenations of prochiral enamides have been extensively studied and excellent results have been frequently achieved, the catalytic asymmetric hydrogenations of 2-arylacrylic acids have been less successful. Until recently most catalyst systems gave only moderate optical yields for the 2-arylpropionic acid products (77). An important breakthrough in the study of these reactions was reported by Noyori et al. By using Ru(BINAP)(OAc)2 as a catalyst precursor, these researchers obtained excellent optical yields in the asymmetric hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic acid (72). 

The ultimate goal in most industrial research is to develop economically attractive processes or products. The technology of asymmetric hydrogenation of 2-arylacrylic acids is probably most useful for the production of naproxen and S-ibuprofen. Naproxen is currently one of the top ten prescription drugs in the world S-ibuprofen is the active isomer in the popular anti-inflammatory drug ibuprofen. Figures 5 and 6 summarize two commercially feasible processes for the manufacturing of these products. 

J. Asymmetric Hydrogenation of 2-Arylacrylic Acids Catalyzed by Immobilized Ru-BINAP Complex in 1 -n-Butyl-3-Methylimidazolium Tetrafluoroborate Molten Salt, Tetrahed. Asymm. 1977, 8, 177-179. 

Table 1 The Rh(/ -SpirOP) -catalyzed asymmetric hydrogenation of (Z)-2-acetamido-3-arylacrylic acids ...

Ruthenium-based asymmetric hydrogenation of a-arylacrylic acids and P-keto esters uses the bipyridylbisphosphine 98 (and its enantiomer). 

Chauvin et al. reported the asymmetric hydrogenation of acetamidocinnamic acid to (S)-phenylalanine with a cationic chiral rhodium catalyst in [C4-mIm][SbFg] ionic liquid, more recently the 2-arylacrylic acid has been produced with a reasonable 64% yield using a chiral ruthenium catalysts in [C4-mIm][BF4] ionic liquids. Palladium catalysts " immobilized in an ionic liquid-polymer gel membrane containing either [C2-mIm][CF3S03] or [C2-mIm][BF4] have also been reported as catalysts for heterogeneous hydrogenation reactions. 

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