Rhodium hydrogenation catalysts, enantiomeric

In 1968, Knowles et al. [1] and Horner et al. [2] independently reported the use of a chiral, enantiomerically enriched, monodentate phosphine ligand in the rhodium-catalyzed homogeneous hydrogenation of a prochiral alkene (Scheme 28.1). Although enantioselectivities were low, this demonstrated the transformation of Wilkinson s catalyst, Rh(PPh3)3Cl [3] into an enantioselective homogeneous hydrogenation catalyst [4]. 

Another interesting issue is the possibility of creating optically active compounds with racemic catalysts. The term chiral poisoning has been coined for the situation where a chiral substance deactivates one enantiomer of a racemic catalyst. Enantiomerically pure (R,R)-chiraphos rhodium complex affords the (iS )-methylsuccinate in more than 98% ee when applied in the asymmetric hydrogenation of a substrate itaconate.109 An economical and convenient method... 

With a rhodium complex catalyst containing a chiral ligand dispersed in [BMIM]SbFg, the enantioselective hydrogenation of a-acetamidocinnamic acid to (5)-phenylalanine was achieved with 64% enantiomeric excess 112). [RuCl2( S)-BINAP]2 NEt3 in [BMIM]BF4 for (5)-naproxen synthesis gave 80% ee from 2-(6-methoxy-2-naphthyl) acrylic acid and isopropyl alcohol 214). 

Enol acetates and corresponding derivatives constitute another class of unsaturated compounds that can advantageously be hydrogenated with high enantiomeric excess. This reaction is related to the enantioselective reduction of ketones. Acylated enol carboxy-lates (as an equivalent of a-keto carboxylic acid) can likewise be successfully reduced with rhodium(I) catalysts based on (5,5)-ethyl-DuPHOS (eq 8). Subsequent deprotection of the hydroxyl group or reduction of the carboxylic acid derivatives so obtained deliver chiral a-hydroxy carboxylates and 1,2-diols, respectively. 

Work on the candoxatril precursor 11 [16] gave an insight into the importance of substrate purity for efficient hydrogenation using rhodium DuPHOS catalyst systems. The asymmetric hydrogenation of 11 with rhodium Me-DuPHOS furnished the desired intermediate 12 in excellent enantiomeric excess and yield (Fig. 9). 

Unlike most rhodium homogeneous catalysts, the ruthenium(BlNAP) series is very effective for the asymmetric hydrogenation of functional ketones48. This leads to a number of experimental circumstances where the directing effect of substituents is brought into play. One of the most commonly used examples of asymmetric ketone hydrogenation is that of /1-keto esters. Diketone reduction with ruthenium[(5)-BINAP] demonstrates the high enantiomeric purity due to double asymmetric induction. 

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 hydrogenation of (Z)-a-Af-acetamidocinnamic acid in ethanol-toluene with complexes 30 and 31 led to complete conversion. It was observed that the ratio of the two solvents plays an important role in the obtained enantiomeric excess of the reaction (Table 22.9). For 30, an increase in the ee was observed with decreasing ethanol content, whereas for 31 the reverse behavior was noted. For (R,R,R)-31 complex an ee of ca. 80% was obtained at an ethanol-toluene ratio of 2/1. This value is comparable with literature values for the rhodium-DIOP catalyst, and together with the solvent-dependent behavior of 31, it is in agreement with the assumed dissociation mentioned above [44]. 

Asymmetric hydrogenation has been achieved with dissolved Wilkinson type catalysts (A. J. Birch, 1976 D. Valentine, Jr., 1978 H.B. Kagan, 1978). The (R)- and (S)-[l,l -binaph-thalene]-2,2 -diylblsCdiphenylphosphine] (= binap ) complexes of ruthenium (A. Miyashita, 1980) and rhodium (A. Miyashita, 1984 R. Noyori, 1987) have been prepared as pure atrop-isomers and used for the stereoselective Noyori hydrogenation of a-(acylamino) acrylic acids and, more significantly, -keto carboxylic esters. In the latter reaction enantiomeric excesses of more than 99% are often achieved (see also M. Nakatsuka, 1990, p. 5586). 

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