Synthesis of Substituted Oxazoles from N‐Acyl‐β‐hydroxyamino Acid Derivatives

Several N‐acyl‐β‐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 I2/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 β‐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 β,β‐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.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)