Four-component Synthesis of 1,3,4-Oxadiazole Derivatives from (N-Isocyanimino)triphenylphosphorane, (E)-Cinnamic Acids, Acetaldehyde and Secondary Amines

Abstract

The 1 : 1 iminium intermediate, generated by the addition of a secondary amine to acetaldehyde is trapped by the (N-isocyanimino)triphenylphosphorane in the presence of an (E)-cinnamic acid derivative, leading to the formation of the corresponding iminophosphorane intermediate. Disubstituted 1,3,4-oxadiazole derivatives are formed via intramolecular aza-Wittig reaction of the iminophosphorane intermediates. The reactions were completed under neutral conditions at room temperature, and the corresponding disubstituted 1,3,4-oxadiazole derivatives were produced in excellent yields.

One Reacts as Two: Applications of N-Isocyaniminotriphenylphosphorane in Diversity-Oriented Synthesis

“…The procedure is fast, high yielding, and very clean, as the only byproducts are water and TPPO. Very soon, the scope of the reaction was extended to the use of cinnamic, − phenylacetylene, − and peptidic , acids, while primary ,− and peptidic amines , also participate, although giving slightly lower yields. Substituted benzyldehydes, , aromatic dialdehydes, furfural, acetaldehyde, , and cinnamaldehyde , readily react as carbonyl components.…”

“…Very soon, the scope of the reaction was extended to the use of cinnamic, − phenylacetylene, − and peptidic , acids, while primary ,− and peptidic amines , also participate, although giving slightly lower yields. Substituted benzyldehydes, , aromatic dialdehydes, furfural, acetaldehyde, , and cinnamaldehyde , readily react as carbonyl components. On the other hand, ketones are restricted to be cyclic ,− or electron-deficient α-halo ketones, , α-acyl­(thi)­oxy propanones, ,,, and biacetyl …”