Hydrogenation of unsaturated amino acids

Scheme 6.2 Asymmetric hydrogenation of unsaturated amino acid derivatives as a model reaction for micellar catalysis using amphiphilic block copolymers.

Pracejus was fascinated by the idea of functionalizing cellulose as the cheapest chiral material and to use it in this form as a carrier for monovalent rhodium for asymmetric hydrogenation. Rh was shown by Wilkinson to be useful as a catalyti-cally active central metal in phosphane complexes. However, the catalytic activities of the new cellulose immobilized complexes in the hydrogenation of unsaturated amino acid precursors were low and the enantioselectivities did not exceed 35%... 

Surprisingly, in the hydrogenation of unsaturated amino acid derivatives catalyzed by a chiral rhodium complex in water, these disadvantages are overcome by the addition of micelle-forming surfactants [48]. The mixture was solubilized by... 

The consumption of electrons in the reduction processes observed with protein can be considered to be due to the saturation of unsaturated amino acids, splitting of disulfide bridges, hydrogenation of electroactive disulfide linkages, and in general, reaction with any electroactive R group from amino acid residues. One reduction reaction shown to occur with proteins is (46),... 

The effects of temperature on enantioselectivities have been examined using a Rh-Et-DuPhos catalyst in both MeOH [56d] and THF [144]. With /5-dehydro-amino acid derivative 73 in MeOH, an increase in temperature was found to have a slight beneficial effect for both ( ) and (Z)-isomers over a 70°C range, with maximum values being observed between 0°C and 25°C. In THF, however, the effect is much more pronounced, especially for the (Z)-isomer which varies in selectivity from 65% ee at 10 °C to 86% ee at 25 °C. Interestingly, when substrate 72 was reduced with a Rh-Et-BPE catalyst in THF, this temperature dependence on enantioselectivity for the (Z)-isomer was most apparent, the se-lectivities varying from 43% ee (10°C) to 90% ee (40°C). Examination of these results also seemed to indicate that the hydrogenation of /9-dehydroamino acid derivatives follows an unsaturated pathway (vide supra) [144]. 

A fi-keto-bis-a-amino acid derivative 267 is a common precursor in these syntheses (Scheme 57), obtained by asymmetric Schollkopf alkylation <1994TL4091>, by Claisen condensation of glutamic acid precursors <1997TL6483, 1998JOC5937>, or by hydrogenation of bis-a,/3-unsaturated amino acid derivatives <2001TL3159>. 

TABLE 7.45. AMINO ACID, AMINO ESTER AND AMINO ALCOHOL DERIVATIVES FROM HYDROGENATION OF UNSATURATED 5(4//)-OXAZOLONES... 

The preparation of the first unsaturated azlactone was reported in 1883 by Plochl/40 who condensed benzaldehyde with hippuric acid in presence of acetic anhydride. This approach was later used by Erlenmeyer/41 who extended the procedure to include other aldehydes and also established the usefulness of azlactones as intermediates in the synthesis of DHAs. The method involves the condensation of an A-acylglydne 4 with aldehydes and ketones in the presence of acetic anhydride and anhydrous sodium acetate (Scheme 2)J41 t5l Other catalysts such as copper(II) acetate/46 lead acetate/47,48 potassium carbonate/49 or potassium hydrogen carbonate 50 have also been used. The reaction proceeds via formation of an azlactone 5, which then condenses with the appropriate aldehyde or ketone to give unsaturated azlactone 6. Reaction of 6 with a nucleophile such as OH, OR, or NHR leads to the corresponding A-acyl-DHA derivatives 7. Reaction with the sodium salt of an amino acid gives a DHA containing dipeptide acid. 51 ... 

The rhodium-chiral phosphine catalyzed asymmetric hydrogenation of protected enam-ides, and other unsaturated amino acid derivatives (equation 85), gave almost 100% ee of the corresponding chiral a-amino acid derivative343,344. 

Hypothesizing that primary amine catalysts, due to their reduced steric requirements, might be suitable for the activation of ketones, we studied various salts of a-amino acid esters. (For pioneering use of primary amine salts in asymmetric iminium catalysis involving aldehyde substrates, see Ishihara and Nakano 2005 Sakakura et al. 2006 for the use of preformed imines of a, 3-unsaturated aldehydes and amino acid esters in diastereoselective Michael additions, see Hashimot et al. 1977.) We have developed a new class of catalytic salts, in which both the cation and the anion are chiral. In particular, valine ester phosphate salt 35 proved to be an active catalyst for the transfer hydrogenation of a variety of a, 3-unsaturated ketones 36 with commercially available Hantzsch ester 11 to give saturated ketones 37 in excellent enantiose-lectivities (Scheme 28 Martin and List 2006). 

Another reaction where amino acids play a key role is the Julia-Golonna epoxidation of a,P-unsaturated ketones [52], which involves the use of a catalytic amount of polymeric amino acids, able to catalyze the Weitz-Scheffer epoxidation of chalcone using basic hydrogen peroxide, with high enantioselectivity (Scheme 8.17 Equation a). 

Asymmetric catalysis by low-valent transition-metal complexes has enormous potential for organic chemistry, but many of its present limitations must be overcome before this can be realized. With existing ligands, hydrogenation of enamides and certain unsaturated carboxylic acids is optically efficient, as is the hydrogenation of ct-amino ketones(58),... 

Catalytic hydrogenation of unsaturated nitrogen heterocycles plays an important role in the synthesis of nitrogen-containing natural products such as alkaloids and amino acids. 

Another approach that has been well documented and has been used at scale is asymmetric hydrogenation. In this case, an enamide is reduced to afford a derivative of the amino acid. Because hydrogen is added across the unsaturation, the method can only be applied to monosubstituted a-amino acids (route f). 

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