Reductions 5 -oxazolones. unsaturated

Catalytic hydrogenation of the exocychc double bond of several oxazolones 611, in the presence of acetic acid, gives a-acylamino alcohols 613 via the saturated derivatives 612 (Scheme 7.196). Selected examples of amino acid derivatives and amino alcohols available from reduction of unsaturated oxazolones are shown in Table 7.45 (Fig. 7.56). 

The azlactones of a-benzoylaminocinnamic acids have traditionally been prepared by the action of hippuric acid (1, Ri = Ph) and acetic anhydride upon aromatic aldehydes, usually in the presence of sodium acetate. The formation of the oxazolone (2) in Erlenmeyer-Plochl synthesis is supported by good evidence. The method is a way to important intermediate products used in the synthesis of a-amino acids, peptides and related compounds. The aldol condensation reaction of azlactones (2) with carbonyl compounds is often followed by hydrolysis to provide unsaturated a-acylamino acid (4). Reduction yields the corresponding amino acid (6), while drastic hydrolysis gives the a-0X0 acid (5). ... 

One strategy to prepare saturated 5(4//)-oxazolones from unsaturated oxazo-lones takes advantage of the reactivity of the exocyclic double bond. In this context, numerous reactions have been explored including reductions, Michael reactions, cycloaddition reactions, and many others. These reactions will be discussed in the context of the reactivity of the exocyclic double bond of the unsaturated oxazolones and will be described in Section 7.4.3. 

TABLE 7.41. iV-ACYLAMINO ACID AMIDES FROM REDUCTIVE AMINOLYSIS OF UNSATURATED 5(4i7)-OXAZOLONES... 

Fluorination of unsaturated 5(47/)-oxazolones 758 affords the expected difluori-nated derivatives 759. Basic hydrolysis of 759 yields a p-fluoro-a-keto acid 760 that is reductively aminated to give an e t/jw-p-fluoro-a-amino acid 761... 

H)-Oxazolones react readily with nucleophiles, C(5) and C(2) be ing possible sites for attack, and, in the case of unsaturated azlactones, C(a) as well (see 199-201). It has been proved by using water labelled with lsO that the acid-catalyzed hydrolysis of unsaturated azlactones proceeds by alkyl-oxygen fission (equation 42). The formation, hydrolysis and reduction of 4-methylene-5(4H)-oxazolones is a well-established method for the synthesis of a-amino acids, e.g. phenylalanine (equation 43). The addition of hydrazoic acid to 5(4H)-oxazolones without methylene groups at C(4) likewise occurs exclusively at C(2) to yield tetrazoles by ring-opening and recyclization (equation 44). 

Through a similar reaction sequence, fluorinated tryptophan 187 was synthesized. Condensation of aldehyde 175 with A-benzoyl glycine afforded oxazolone 184, which was converted into unsaturated acid 185. Reduction of 185 by hydrogen and subsequent acid-catalyzed hydrolysis gave fluorinated tryptophan 187 in good total yield [54]. 

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