One-pot synthesis of fully substituted 1,3,4-oxadiazole derivatives from (E)-Cinnamic Acid, Acetaldehyde and N-isocyanimino)triphenylphosphorane

In recent years, multicomponent reactions (MCRs) have become important tools in modern preparative synthetic chemistry because these reactions increase the efficiency by combining several operational steps without any isolation of intermediates or changes of the conditions [1]. This principle, therefore, is highly efficient in terms of time as well as resources [2]. Among the known multicomponent reactions to date, the most valuable reactions are those based on isocyanides [1,2]. Isocyanide-based multicomponent reactions (abbreviated to IMCRs by Ugi and Dömling) by virtue of their synthetic potential, their inherent atom efficiency, convergent nature, ease of implementation, and the generation of molecular diversity, have attracted much attention because of the advantages that they offer to the field of combinatorial chemistry [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 [2-3], we wish to report the synthesis of a new class of 1,3,4-oxadiazole derivatives 4 by a novel tree-component condensation of Acetaldehyde 1, derivatives from (E)-Cinnamic Acid 2 and (N-isocyanimino)triphenylphosphorane 3 in excellent yields under neutral conditions (Scheme 1).