Synthesis of 2,5-Substituted 1,3,4-Oxadiazoles via a Tandem Reaction Involving a Cobalt-Catalyzed Carbene Transfer to N-Isocyaniminotriphenylphosphorane

A cobalt(II)-catalyzed three-component synthesis of 2,5-substituted 1,3,4-oxadiazoles using N-isocyaniminotriphenylphosphorane (NIITP), diazo compounds, and carboxylic acids has been developed. The tandem reaction involves a carbene transfer to NIITP, followed by the addition of the carboxylic acid to the in situ-formed ketenimine and a subsequent intramolecular aza-Wittig reaction. The protocol tolerates a broad range of carboxylic acids and diazoacetates. This includes medicinally relevant carboxylic acids that were successfully converted into their corresponding 1,3,4-oxadiazole bioisosteres. Postfunctionalization extends the applicability of this three-component reaction.