5-Oxazolone ring opening

In a similar way, propargyl esters of A -benzoyl-a-amino acids have been converted into a-allenyl-a-amino acid esters 113 by cyclization to oxazoles 111 followed by Claisen rearrangement to the 4-allenyl-2-phenyl-5(4//)-oxazolones 112. Oxazolone ring opening with methanol then afforded 113 (Scheme 7.32). ... 

Alkylation. Saturated 5(47/)-oxazolones are readily available compounds that can be easily obtained from a wide variety of natural amino acid derivatives. These heterocyclic compounds can be considered as nucleophilic synthons of a-amino acids and their most exploited reactivity, apart from oxazolone ring opening, is the reaction at C-4 with a variety of electrophiles. 

Rhodanines have been obtained from 3-formyI-lO-methylpheno-thiazine and its 5,5-dioxide. From these two aldehydes and also from 2-formyl- and 2-formyl-lO-methylphenothiazine, azlactones have been prepared, and their physical properties and oxazolone ring-opening reactions have been investigated. ° ... 

Alkylidene- and 4-arylidene-5(4/0-oxazolones, which are versatile intermediates for the synthesis of didehydroamino acids, offer another site, Ca, for reaction. The propensity for nucleophiles to attack at this position has been exploited in the synthesis of other heterocycles. A -Acyldithio-carbamic acids add in Michael fashion, and the intermediates undergo cyclization with concomitant oxazolone ring opening to furnish 2-thioxo-l,3-thiazin-4-ones (87) (Scheme 27) <92S919>. 

The behavior of unsaturated azlactones with organometallic reagents has been studied in detail. Arylmagnesium halides and phenyllithium attack 4-arylidene-5-oxazolones at the carbonyl carbon to give ring-opened amido tertiary alcohols (26) and oxazolines (27) (by ring closure), usually as mixtures [Eq. (17)]. The nature of the... 

In contrast to these ring-opening reactions, it was observed by Horner and Schwahn that 4-arylidene-(isopropylidene and cyclo-hexylidene)-oxazolones react with alkyl Grignard reagents by conjugate addition to give saturated azlactones 29a as the only products [Eq. (18)]. 

The hetero ring in 4-(l -hydroxyalkylidene)-5-oxazolones is cleaved by alcoholic HCl to form alkyl a-acylaminoacylacetates, which cyclize to oxazole-4-carboxylates [Eq. (25)]. This rearrangement occurs directly in alkali, and a carbon-14 tracer study has substantiated a mechanism involving ring opening followed by the alternative ring closure. ... 

The conversion of a 4-arylazo-5-oxazolone into a 1,2,4-triazole by reaction with a Grignard reagent is mentioned in Section II, B, 3. In HiTnilar fashion, the rearrangement of compound 30 to derivatives of 3-carboxy-l,5-diphenyl-lfl -l,2,4-triazoles (40) proceeds readily in the presence of strong nucleophiles [Eq. (26)]. This transformation undoubtedly occurs by ring opening and dehydrative cychzation, and, indeed, the acyclic amide and hydrazide 41 have been isolated. ... 

The oxazolone 43, prepared by reaction of 0-methylcaprolactim (42) with compound 1, undergoes a ring-opening reaction with methanolic HCl and cyclizes in alkaline medium to 1,5-pentamethyl-ene-2-phenylimidazole-4-carboxylic acid (44), which can be decar-boxylated easily. 

Arylidene-5-oxazolones undergo a ring-opening reaction with aromatic thiols and a second mole of thiol is then incorporated to give products such as 48. ... 

Conjugate addition of strong nucleophiles to the >C=N—C=C< moiety, followed by ring opening of the resulting saturated 5 4H)-oxazolone. Thus, 57 reacts with simple or peptidic amino acid esters [Eq. (31)]. Similarly, 62 gives 63 in methanolic 7i-propylamine, and... 

With monoamines, the oxazolones give the normal ring-opened products, A-TFA amino acid amides, but with aniline both forms... 

A very attractive and efficient method for the synthesis of L-aminoacids via DKR has been reported by Turner et al. [41a,b]. They employed enzyme-catalyzed ring opening of 5(4H)-oxazolones in combination with a catalytic amount of Et3N. The relatively low pKa of the C-4 proton (8.9) of oxazolones facilitates racemization. Hydrolysis of the ester obtained through DKR, followed by debenzoylation, yields L-aminoacids in excellent enantiomeric excess (99.5%) (Figure 4.16). In their initial studies, they employed Rhizomucor miehei lipase (Lipozyme) as the biocatalyst [41]. More recently, they have obtained excellent results employing CALB [41bj. This method has also been employed by Bevinakatti [41c,d] and Sih [41e,fj. 

M Goodman, L Levine. Peptide synthesis via active esters. IV. Racemization and ring-opening reactions of optically active oxazolones. JAm Chem Soc 86, 2918, 1964. 

Certain erythro-2-wamo alcohols such as ( )-ephedrine 150, ( )-A -methyl-ephedrine 151 and ( )-conhydrine 153 are synthesized with complete stereochemical control by the catalytic hydrogenation of the corresponding 4,5-disubstituted 2(3/i)-oxazolone derivatives 22 and 27, followed by ring opening (Fig. 5.37). ... 

Alkoxy-2(3/f)-oxazolones 47 react with aliphatic and aromatic aldehydes in the presence of Lewis acid catalysts to produce alkyl 2-oxazolidinone-4-carbox-ylates 291 ° by successive ring opening and reclosure. 

During investigations of the synthesis of tetracycline ring A analogues, Moska-lyk and co-workers unexpectedly isolated 4(5//)-oxazolones 31 and 33 following reaction of 30 and 32 with sodium ethoxide then chloroacetyl isocyanate. Further reaction of 31 effected ring opening of the 4(5F/)-oxazolone to yield 34 (Scheme 6.11). 

Saturated 2-vinyl-5(47Z)-oxazolones have been widely used as intermediates for the synthesis of polymeric compounds that will be described in Section 7.3.2.9. Apart from these polymerization reactions, the Diels-Alder reactions of 4-sub-stituted-2-vinyl-5(47/)-oxazolones 134 with cyclopentadiene are reported to give norbomenyl oxazolones 135 that are useful to prepare norbornenyl functionalized resins by azlactone ring-opening addition reactions (Scheme 7.39). 

Michael Reaction. 5(47/)-Oxazolones undergo base-catalyzed conjugate addition to activated unsaturated compounds to afford the corresponding C-4 Michael adducts. For example, base-catalyzed addition of a 4-monosubstituted-5(4//)-oxazolone 157 to methyl propiolate yields a mixture of diastereomeric methyl 3-(5-oxo-2-phenyl-2-oxazolin-4-yl)acrylates 158. Hydrolytic ring opening of 158 and subsequent oxidation with lead tetraacetate affords 3-acylacrylates 160... 

It has also been reported that some 4-substimted-5(47/)-oxazolones 166 undergo Michael addition to triphenylvinylphosphonium bromide to give the corresponding 4,4-disubstituted-5(47/)-oxazolones 167 from which ring opening... 

When carbonyl compounds are used as electrophiles reaction with 4-monosub-stituted-5(4//)-oxazolones affords substituted serines after subsequent hydrolytic ring opening of the initial aldol product. As an example, 4-methyl-2-phenyl-5(4//)-oxazolone 193, prepared from alanine, reacts with benzaldehyde in a base-catalyzed addition to give, after hydrolysis, a 3 1 mixture of threo- and... 

Finally, cationic ring-opening polymerization of 2-aIkoxy-5(4//)-oxazolones has been used to prepare poly iV-alkoxycarbonyl amino acids. The polymerization was found to be dependent on the nature of the amino acid side chain and the substituent on C-2. 

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