Asymmetric hydrogenation of dehydroamino acid derivatives

Hydrogenation Easily prepared monodentate phosphoramidite ligands containing a BINOL residue are employed in conjunction with (cod)2RhBp4 in asymmetric hydrogenation of dehydroamino acid derivatives and a-substituted acrylic esters (ee > 99% reachable). 

The asymmetric hydrogenation of dehydroamino acid derivatives is stiU a popular research area. For the synthesis of N-acetyl o-alanine methyl ester, the hydrogenation is carried out in supercritical carbon dioxide with catalyst 76. On the other hand, the preparation of protected L-valine and related compounds requires the hydrogenation of a tetrasubstituted double bond. An Rh catalyst with ligand 77 is well suited for this... 

General procedure for asymmetric hydrogenation of dehydroamino acid derivative ... 

Based on the concept mentioned above, Brown realized the asymmetric deactivation of a racemic catalyst in asymmetric hydrogenation (Scheme 9.18) [35]. One enantiomer of (+)-CHIRAPHOS 28 was selectively converted into an inactive complex 30 with a chiral iridium complex 29, whereas the remaining enantiomer of CHIRAPHOS forms a chiral rhodium complex 31 that acts as the chiral catalyst for the enantioselective hydrogenation of dehydroamino acid derivative 32 to give an enantio-enriched phenylalanine derivative... 

Asymmetric hydrogenation of N-acyl-x-aminocinnamic acids. Rh(I) complexes with either 1 or 2 attached to polymers with suitable swelling characteristics are very effective for asymmetric hydrogenation of dehydroamino acids. Optical yields of about 90% are possible. As expected, polymer-bound Rh(I)-l results in (R)-amino acid derivatives, whereas polymer-bound Rh(I)-2 results in (S)-amino acid derivatives. 

In the same way, cationic complexes of amine derivatives of BDPP and CHIRA-PHOS were prepared which showed unlimited solubility in water and negligible solubility in common organic solvents. They were used in asymmetric hydrogenation of dehydroamino acids and provided modest to high enantioselectivities [20 b], The presence of the dimethylamino group in the DIOP derivative resulted in a reversal in the observed dominant product antipode, which was attributed to a change in the preferred ligand conformation. 

Amino-derived BDPP (2,4-bis[diphenylphosphino]pentane) has been used in asymmetric hydrogenation catalysis [15-17] (cf. Sections 6.2 and 6.9). NMR analysis showed that a ten-fold excess of HBF4 is sufficient to protonate reversibly all four amino groups in the [Rh(diene)(BDPP)]BF4 complex. Recycling of the catalyst after enantioselective hydrogenation of dehydroamino acid derivatives in methanol is achieved by acidification with aqueous FIBF4 followed by extraction of the product with Et20. Immobilization of the protonated BDPP rhodium complex on a Nafion support has been studied as well [18]. 

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. 

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