N-Acyl-dehydroamino acids

Rhodium-catalyzed enantioselective hydrogenation of N-acyl enamides provides access to enantioenriched amides which can be hydrolyzed to the free amines. The synthesis of the substtates is considerably less sttaightforward than that of N-acyl dehydroamino acids, which explains the smaller number of reports devoted to N-acyl enamides. 

TABLE 7.39 N-ACYL DEHYDROAMINO ACIDS AND ESTERS FROM HYDROLYSIS AND ALCOHOLYSIS OF UNSATURATED 5(4//)-OXAZOLONES, 229... 

Peptide formation by acylation of amino acid esters with N-acyl-dehydroamino acids can be carried out by employing activated derivatives of the latter. Suitable derivatives are the N-carboxy-a-amino acid anhydrides (226), or mixed anhydrides (257, 314). Coupling with DCCD/ N-hydroxysuccinimide is also applicable (314B). 

Table 28.7 Enantioselective hydrogenation of N-Acyl-jS-dehydroamino acid esters.

Hydrazinolysis products obtained from oxazolones 528 are versatile synthetic intermediates and can be further elaborated to a variety of different heterocycles depending on the substituents and on the experimental conditions. For example, N-aminoimidazolones 529, isolated from reaction of 528 and hydrazine, have been acylated ° or condensed with carbonyl compounds to produce 530 and 531, respectively. On the other hand, ring-opening 528 with hydrazine affords a dehydroamino acid hydrazide 532. Condensation of 532 with aldehydes yields a hydrazone 533 that can be cyclized to an A -iminoimidazolone 534 (Scheme 7.168). ... 

Unfortunately, A-(9-fluorenylmethoxycarbonyl)aziridine-2-carboxylic acid cannot be used in peptide synthesis, since N-deprotection of the respective peptides with secondary amines leads to oxazoline or dehydroamino acid side products. Similarly, N-(tert-butoxy-carbonyl)aziridine-2-carboxylic acid is inappropriate due to the instability of the aziridine moiety to TFA treatment. Attempts to convert A-tritylaziridine-2-carboxylic acid into homogenous and stable active esters as useful intermediates in peptide synthesis leads to positive results only in the case of the pentafluorophenyl ester. 47 Consequently, this active ester seems to be the method of choice for acylating peptides. The related Abhydroxysuc-cinimide and A-3-hydroxy-4-oxo-3,4-dihydro-l,2,3-benzotriazine ester could not be isolated in pure form and have therefore been used as crude products. 47 Access to 2-carbonylazir-idine peptides is also possible by carbodiimide-mediated coupling. Additionally, alkylamides of A-tritylaziridine-2-carboxylic acid are prepared by the azide method,1 5 yet this method fails in peptide coupling steps. 85 ... 

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. 

Schmidt, U., Lieberknecht. A.. Schanbacher. U.. Beuttler. T.. and Wild, J., Facile preparation of N-acyl-2-(diethoxyphosphoryl)glycine esters and then- use in the synthesis of dehydroamino acid esters, Angew. Chem. Int. Ed. Engl.. 21. 776. 1982. 

Imide formation. N-Carboxy-a-dehydroamino acid anhydrides couple with. V-protected amino acids. Such anhydrides usually serve as acylating agents for amines. 

Shin, C., K. Nanjo, E. Ando, and J. Yoshimura a,p-Unsaturated Carboxylic Acid Derivatives. VI. New Synthesis of N-Acyl-a-dehydroamino Acid Esters. Bull. Chem. Soc. Japan 47, 3109 (1974). 

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