Enantiopure unsaturated amino acids

VI. ENANTIOPURE UNSATURATED AMINO ACIDS AS BUILDING BLOCKS... 

Enantiopure unsaturated amino acids are ideally suited for further selective transformations. In this section some selected examples are given. Radical additions will lead to enantiopure sulfur-containing amino acids. Ring-closing olefin metathesis will give cyclic amino acids, whereas Pd-catalyzed oxy palladation, amido palladation, and cross-coupling will lead to a vast array of enantiopure heterocyclic compounds. 

Hydrogenation of -substituted ( )-p-(acylamino)acrylates catalyzed by the BINAP-Ru es P-amino acid derivatives with high enantiopurities (Scheme 1.9) [8S]. The Z double-bond isomers that have an intramolecular hydrogen bond between amide and ester groups are more reactive but are hydrogenated with poor enantioselectivity. The sodium or triethylammonium salts of the unsaturated acid are hydrogenated in water containing a sulfonated p-Ibl-MeO-BIPHEP-Ru ditrifluoroacetate complex with an S/C of KKX)-10,000 and an up to 99% optical... 

Finally, the synthesis of a variety of unsaturated (alkenyl and alkynyl) amino acids is described. Those trifunctional amino acids are ideal starting materials for a series of highly functionalized, conformationally restricted cyclic amino acids using either Pd catalysis or Ru-catalyzed ring-closing metathesis. The resulting enantiopure functionalized cyclic amino acids appear to be versatile scaffolds in combinatorial approaches. 

Cycloadditions. [2+1], [2 + 2], and [4 + 2] cycloadditions with electrophilic reactants such as carbenes (eq 5), tetracya-noethylene (eq 6), and a-keto-, Y-unsaturated nitriles (eq 7) lead to interesting products which are all enantiopure see, for instance, the 5-amino-6-hydroxy-2-keto acid (5). 

Chen and coworkers have reported a new domino Michael-Michael addition reaction between a,a-dicyanoalkene [26] derived from cyclohexanone and benzyli-deneacetone, resulting in a stepwise [4 + 2]-type cycloaddition to afford almost enantiopure bicyclic adduct 15. In contrast to the completely inert function of secondary ammonium salt, a primary amine, 9-amino-9-deoxyepiquinine lo [27], in combination with trifluoroacetic acid, was found to be highly efficient in the activation of the a, 3-unsaturated ketone by tandem iminium-enamine catalysis (Scheme 10.21) [28],... 

Other electrophiles, such as Michael acceptors, can also be involved in the a-alkylation step. This has been exploited in the conjugate addition of enantiopure lithium amides 60 to unsaturated esters 61, followed by trapping of the resulting enolate with alkylidene malonates. This constitutes a useful methodology for the asymmetric synthesis of p-amino-a-substituted carboxylic acid derivatives 62 (Scheme 11.24) [65]. 

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