Synthesis of 5-Methoxy-4-benzyloxazoles from Tyrosine and m-Tyrosine under Bischler-Napieralski Conditions*

Oxazoles are interesting from both a pharmacological and a chemical point of view. For example, they are known to interact with various proteins such as sodium-dependent excitatory amino acid transporters [1] or DNA repair protein OG-alkylguanine DNAalkyl-transferase [2], and furthermore, they display bacteriostatic [3] and antiinflammatory activity [4]. Additionally, oxazoles provide useful entries into the synthesis of other heterocyclic compounds such as pyridines [5], α-amido oximes [6], and azlactones [7]. Since the seminal finding by Reeve and Paré [8] that acylamidophenylalanine esters 1 can undergo a cyclization to the oxazole 3 instead of the desired dihydroisoquinolines 2 under Bischler-Napieralski conditions [9] (Scheme 1), this reaction was observed by several groups [6, 10]. The electronic influence of substituents at the phenyl moiety has been explored to some extent [10b, 10c], however, substituent effects at the amide function remained unclear. Herein we wish to disclose our studies on this reaction in more detail.