Dehydroamino acids, asymmetric hydrogenation

Besides enzymatic reactions, many homogenously catalyzed hydrogenations follow Scheme 2.2. An example is the asymmetric hydrogenation dehydroamino acid derivatives with rhodium or ruthenium catalysts. On the basis of Scheme 2.2 the following rate equation can be derived ... 

Additionally, a Rh(I) dissacharide system has also been used to hydrogenate dehydroamino acids and their esters asymmetrically in water and in a biphasic aque-ous/organic medium [34]. In one example, a-acetamidocinnamate was completely reduced (100% conversion), rendering the (S) product in 90% ee in one hour using 1 mol% of the catalyst in water. Other ligand frameworks coordinated to Rh(I)... 

In 2006, Berens et al. reported the synthesis of novel benzothiophene-based DuPHOS analogues, which gave excellent levels of enantioselectivity when applied as the ligands to the asymmetric rhodium-catalysed hydrogenation of various olefins, such as dehydroamino acid derivatives, enamides and itaco-nates (Scheme 8.10). ... 

In 1998, Ruiz et al. reported the synthesis of new chiral dithioether ligands based on a pyrrolidine backbone from (+ )-L-tartaric acid. Their corresponding cationic iridium complexes were further evaluated as catalysts for the asymmetric hydrogenation of prochiral dehydroamino acid derivatives and itaconic acid, providing enantioselectivities of up to 68% ee, as shown in Scheme 8.18. 

Enantioselectivities of up to 47% ee were reported by Ruiz et al. in 1997 for the asymmetric hydrogenation of various prochiral dehydroamino acid derivatives and itaconic acid by using iridium cationic complexes of the novel chiral... 

The use of rhodium catalysts for the synthesis of a-amino acids by asymmetric hydrogenation of V-acyl dehydro amino acids, frequently in combination with the use of a biocatalyst to upgrade the enantioselectivity and cleave the acyl group which acts as a secondary binding site for the catalyst, has been well-documented. While DuPhos and BPE derived catalysts are suitable for a broad array of dehydroamino acid substrates, a particular challenge posed by a hydrogenation approach to 3,3-diphenylalanine is that the olefin substrate is tetra-substituted and therefore would be expected to have a much lower activity compared to substrates which have been previously examined. 

Table 2 Asymmetric hydrogenation of / ,/3-dimethyl a-dehydroamino acid esters...

Compared to the great advance achieved in the Rh-catalyzed asymmetric hydrogenation, the Ru-catalyzed asymmetric hydrogenation of ct-dehydroamino acid derivatives takes a different mechanistic pathway,215 and little success has been made. 

Complexes containing one binap ligand per ruthenium (Fig. 3.5) turned out to be remarkably effective for a wide range of chemical processes of industrial importance. During the 1980s, such complexes were shown to be very effective, not only for the asymmetric hydrogenation of dehydroamino adds [42] - which previously was rhodium s domain - but also of allylic alcohols [77], unsaturated acids [78], cyclic enamides [79], and functionalized ketones [80, 81] - domains where rhodium complexes were not as effective. Table 3.2 (entries 3-5) lists impressive TOF values and excellent ee-values for the products of such reactions. The catalysts were rapidly put to use in industry to prepare, for example, the perfume additive citronellol from geraniol (Table 3.2, entry 5) and alkaloids from cyclic enamides. These developments have been reviewed by Noyori and Takaya [82, 83]. 

Under isobaric conditions (k2 = k2 H2 J. many hydrogenations exactly follow this model. The classical example is the asymmetric hydrogenation of prochiral dehydroamino acid derivatives with Rh or Ru catalysts [21]. 

Blackmond et al. investigated the influence of gas-liquid mass transfer on the selectivity of various hydrogenations [39]. It could be shown - somewhat impressively - that even the pressure-dependence of enantioselectivity of the asymmetric hydrogenation of a-dehydroamino acid derivatives with Rh-catalysts (as described elsewhere [21b]) can be simulated under conditions of varying influence of diffusion These results demonstrate the importance of knowing the role of transport phenomena while monitoring hydrogenations. 

In the case of the a-dehydroamino acid (Fig. 10.23, right), it could be shown by using low-temperature NMR spectroscopy that the isolated crystals correspond to the major substrate complex in solution. However, according to the major-minor concept (see Scheme 10.2), it does not lead to the main enantiomer [63]. On the contrary, it could be proven unequivocally for various substrate complexes with yS-dehydroamino acids that the isolated substrate complexes are major-substrate complexes. Surprisingly, they also gave the main enantiomer of the asymmetric hydrogenation, which would not be expected on the basis of... 

In general, applications of AMPP have concentrated on the asymmetric hydrogenation of functionalized olefins, especially dehydroamino acids. Among... 

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