Racemization 4-alkyl-5 -oxazolones

To minimize racemization, the use of nonpolar solvents, a minimum of base, low reaction temperatures, and carbamate protective groups (R = O-alkyl or O-aryl) is effective. (A carbamate, R = O-r-Bu, has been reported to form an oxazolone that appears not to racemize during base-catalyzed coupling.) ... 

Carbamates can be used as protective groups for amino acids to minimize racem-ization in peptide synthesis. Racemization occurs during the base-catalyzed coupling reaction of an A-protected, carboxyl-activated amino acid and takes place in the intermediate oxazolone that forms readily from an A-acyl-protected amino acid (R = alkyl, aryl) ... 

Racemization is not encountered when 4-unsubstituted-5(477)-oxazolones or 4,4-disubstituted-5(477)-oxazolones are used as reagents. Indeed, 4-unsubstituted-5(47/)-oxazolones function as glycine synthons in the synthesis of A-acylglycyl-a-amino acids. For example, aminolysis of 2-(trifluoromethyl)-5(47/)-oxazolone with a-methylphenylalanine affords A-(trifluoroacetyl)glycyl-a-methylphenylalanine. 4,4-Disubstituted-5(4//)-oxazolones, readily available by alkylation of the monosubstituted derivatives, are very useful intermediates in the synthesis of peptides that incorporate ot,ot-disubstituted amino acids. As an example, 4-(aryl-methyl)-2-phenyl-4-(trifluoromethyl)-5(4//)-oxazolones 260 are key intermediates... 

The authors applied the same synthetic strategy to racemic 4-alkyl -(iodo-methyl)-2-phenyl-5(4/ )-oxazolones 266 and obtained a diastereomeric mixture of oxazolines 267 and 268 (Scheme 7.86). The diastereoisomers were separated chromatographicaUy and then converted into dipeptides incorporating an a-alkyl-serine residue. ... 

A number of systematic structural analyses have been described for families of saturated oxazolones. First, as mentioned previously, detailed smdies of NMR long-range coupling in 2,4-disubstimted-5(47/)-oxazolones and in 5(27/)-oxazo-lones have been reported." Similarly, detailed NMR studies of the kinetics of racemization of 2,4-disubstimted-5(47/)-oxazolones have been performed. A theoretical study of the spectral-luminescence properties of some 4-alkyl-2-phenyl-5(47/)-oxazolones has been reported and an investigation of the infrared (IR) and Raman spectra of 5(4//)-oxazolones, particularly of the carbonyl group vibration, has been reported. Electron impact mass spectra of saturated 5(47/)-oxazolones have been published. More recently this technique has been used to distinguish between the stereoisomers of some spirocyclopropane oxazolones 352 (Fig. 7.36). Finally, several studies of the HPLC behavior of 5(47/)-oxazolones complete a general view for this family of compounds. " " ... 

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