Ugi/Robinson–Gabriel reactions directed toward the synthesis of 2,4,5-trisubstituted oxazoles

This Letter discloses a novel concise synthesis of a series of 2,4,5-trisubstituted oxazoles via a tandem Ugi/Robinson–Gabriel sequence. Herein, 2,4-dimethoxybenzylamine 1 was used as an ammonia equivalent in combination with arylglyoxal 3 and supporting Ugi reagents, an isonitrile and carboxylic acid. As such the product of the acid treated Ugi intermediate is ideally configured to undergo a Robinson–Gabriel cyclodehydration reaction to yield the desired oxazole scaffold 5.