Synthesis of substituted oxazoles from N-acyl-beta-hydroxyamino acid derivatives

Abstract

Several N-acyl-beta-hydroxyamino acids were prepared and treated with di-tert-butyl dicarbonate in the presence of 4-(dimethylamino)pyridine, followed by treatment with N,N,N',N'-tetramethylguanidine to give the corresponding N-acyldehydroamino acids in good to high yields. These were then treated with I-2/K2CO3 followed by 1,8-diazabicyclo[5.4.0]undec-7-ene. The methyl esters of N-acyldehydroaminobutyric acid gave the corresponding substituted oxazoles in good to high yields. The N-acyldehydrophenylalanines gave 5-phenyloxazole derivatives in low to moderate yields together with beta-iododehydrophenylalanines. Under the same conditions, N-acyldehydroalanines failed to give the corresponding oxazoles. However, when the reaction was carried out in the absence of DBU, it was possible to isolate the beta,beta-diiododehydroalanine derivatives. Although the reason for the different reactivities of the N-acyldehydroamino acids is not completely clear to us, cyclic voltammetry studies showed that the less-reactive derivatives have higher reduction potentials. This suggests that the double bonds in dehydroaminobutyric acid derivatives are more susceptible to electrophilic attack by iodine. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).