Efficient One-Pot Synthesis of Disubstituted 1,3,4-Oxadiazole Derivatives from the Reaction of (N-Isocyanimino)triphenylphosphorane, Acetaldehyde, a Secondary Amine, and an Electron-Poor (E)-Cinnamic Acid

The intramolecular version of the aza-Wittig-type reaction has attracted considerable attention recently because of its high potential for the synthesis of a wide variety of nitrogen heterocycles, which can be attributed, in good measure, to the rapid progress in the preparation of functionalized iminophosphoranes [1]. The nucleophilicity at the nitrogen is a factor of essential mechanistic importance in the use of these iminophosphoranes as aza-Wittig reagents [2]. Iminophosphoranes are important reagents in synthetic organic chemistry, especially in the synthesis of naturally occurring products, compounds with biological and pharmacological activity [1,2]. However, the organic chemistry of (N-isocyanimino)triphenylphosphorane 4 remains almost unexplored. (N-isocyanimino)triphenylphosphorane 4 is expected to have synthetic potential because it provides a reaction system in which the iminophosphorane group can react with a reagent having a carbonyl functionality [3]. In recent years, we have established a one-pot method for the synthesis of organophosphorus compounds [1,3]. As part of our ongoing program to develop efficient and robust methods for the preparation of heterocyclic compounds, we wish to report the synthesis of a disubstituted 1,3,4-oxadiazole derivatives 5 by a four-component condensation of secondary amine 2, acetaldehyde 1, (N-isocyanimino)triphenylphosphorane 4 and an electron-poor (E)-cinnamic acid derivative 3 in excellent yields under neutral conditions.