Mechanistic studies on tandem cascade [4 + 2]/ [3 + 2] cycloaddition of 1,3,4-oxadiazoles with olefins.

The mechanism of the reaction of 1,3,4-oxadiazoles with alkenes (ethylene) and cycloalkenes (cyclobutene, cyclopentene, cyclohexene and cycloocene) have been studied computationally at the DFT M06-2X/6-311G* level. The reaction is found to proceed via a concerted [4 + 2] addition followed by nitrogen extrusion and then [3 + 2] addition in a tandem cascade fashion, which in the case of cycloalkenes leads to exo-fused or endo-fused subframes, the exo of which is kinetically and thermodynamically favored. The [4 + 2] step is the rate-determining step of the reaction. CF as a substituent on the 1,3,4-oxadiazole decreases the activation barriers of the rate-determining step, while COMe on the oxadiazole increases the activation barriers of the rate-determining step, markedly in the case of the reaction with cyclopentene and only marginally in the reactions with ethylene. Increasing temperature decreases the barrier of the rate-determining step and stability of the products but increases the rate of the nitrogen extrusion step. The low barriers of the second and third steps of the reaction compared to the first step means that the intermediates will not be isolated in the reaction, confirming the experimental observations of earlier workers. Based on calculated activation barriers, the reactivity of the various cycloalkenes considered in this study follows the order: cyclooctene > cyclopentene > cyclohexene > cyclobutene which is consistent with the trends in product yields obtained in earlier experimental studies.