5 2// -Oxazolones 4-heteroaryl

The resolution was then based on the enzymatic propanolysis of this derivative in dioxane as solvent. Lip Novozyme 435 selectively cleaves the L-form of the oxazolone producing an L-enriched (81-87% ee) 2-acetamido-3-(heteroaryl)propionic acid propyl ester, the dynamic aspect of the process being based on the continual racemization of the residual oxazolone. The propyl group was then removed with alkali and a second selective enzymatic step to remove the acetyl protecting group with Fluka Acylase 1 produced the L-amino acid at better than 99% ee (Scheme 13). 

The use of 2-(hydroxymethyl)furan or 2-(hydroxymethyl)thiophene as aUyhc alcohols gives rise to a-(trifluoromethyl)-a-(2-heteroaryl)glycine derivatives 125 after hydrolysis of the corresponding oxazolone 124 as shown in Scheme 7.35. ... 

Arylation. Arylation of 2,4-diaryl-5(4//)-oxazolones 170 with activated aryl halides has been reported to proceed under phase-transfer conditions (Scheme 7.51). The yields of 2,4-diaryl-4-(2,4-dinitroaryl)-5(47/)-oxazolones 171 are often modest. Heteroarylation of 170 was accomplished using 2-chloro-3,5-dinitropyridine. Representative examples are shown in Table 7.19 (Fig. 7.21). 

Condensation of an Al -heteroaryl-7/,7/-dimethylformamidine or 7/,Al -diphenyl-formamidine with 2-phenyl-5(47/)-oxazolone 146 gives 4-(aminomethylene)-2-phenyl-5(47/)-oxazolones 207 that are synthetic equivalents of p-amino-a,p-dehy-dro-a-amino acid derivatives 208 (Scheme 7.63). ... 

Transamination reactions have also been described for 4-(aminomethylene)-2-substituted-5(47T)-oxazolones. As an example, displacement of the A-methyl-heteroarylamino group of a 4-[(A-heteroaryl-A-methyl)aminomethylene]-2-phen-yl-5(47T)-oxazolone 420 by an a-amino acid derivative produces p-amino-a,(3-dehydro-a-amino acid precursors 421 (Scheme 7.137). ... 

More drastic hydrolysis conditions of unsaturated oxazolones 448 leads to further hydrolysis of the intermediate 2-acylamino-2-alkenoic acid 449 and produces the corresponding a-keto acids 450. For example, phenylpyruvic acid " and other aryl(heteroaryl)pyruvic acids of biological interest have been obtained in this manner (Scheme 7.148). 

Reaction of a-hydrazinoheterocycles with 4-(hydroxymethylene)-2-phenyl-5(4//)-oxazolone 406 gives rise to A-benzoyl-ot-(heteroaryl)glycinates 563 containing a fused 1,2,4-triazole after oxidative cyclization (Scheme 7.178). ... 

Angew. Chem. Int. Ed. Engl. 44, 3668-3688, 2005 Kent, M. and Tepe, J.J., One-pot Friedel-Crafts/ Robinson-Gabriel synthesis of oxazoles using oxazolone templates, J. Org. Chem. 70, 4211 213, 2005 Movassaghi, M. and Ondrus, A.E., Enantioselective total synthesis of tricyclic myrmicarin alkaloids, Org. Lett. 7, 4423 426, 2005 Paizs, C., Katona, A., and Retey, J., The interaction of heteroaryl-acrylates and alanines with phenylalanine ammonia-lyase form parsley. Chemistry 12, 2739-2744, 2006. Cuprous ions have been observed to promote a Friedel-Crafts acylation reaction (Kozikowski, A.P. and Ames, A., Copper(l) promoted acylation reactions. A transition metal-mediated version of the Friedel-Crafts reaction, J. Am. Chem. Soc. 102, 860-862, 1980). 

DKR of Oxazolones and Oxazinones The spontaneous racemization of several 4-[(heteroaryl)methyl]-2-methyloxazol-5(4//)-ones rac-122 in an organic solvent has permitted the DKR of these substrates using CAL-B as the catalyst, 1-propanol as the nucleophile, and 1,4-dioxane as the solvent (Scheme 57.36). Transesterification reactions were carried out at room temperature, maintaining the... 

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