1,2,4‐ and 1,3,4‐Oxadiazole Synthesis by Palladium‐Catalyzed Carbonylative Assembly of Aryl Bromides with Amidoximes or Hydrazides

Aryl bromides were successfully transformed into their corresponding N,N′ ‐diacylhydrazines via a Pd‐catalyzed carbonylative coupling with acylhydrazines. These reactions employed near‐stoichiometric amounts of carbon monoxide generated ex situ from a non‐gaseous precursor. A range of di(hetero)aryl diacylhydrazines was isolated in good to excellent yields. Furthermore, dehydration conditions were identified that could be used in a compatible one‐pot synthesis of 1,3,4‐oxadiazoles. The applicability of this method towards 13 C‐isotope labeling was also demonstrated, with the production of symmetrical and non‐symmetrical doubly isotopically labeled 1,3,4‐oxadiazoles. Finally, experimental conditions were identified for the carbonylative coupling of aryl bromides with amidoximes and CO producing 1,2,4‐oxadiazoles after spontaneous dehydration. magnified image