A Density Functional Theory Investigation of the Tandem Radical Cyclization of 1-[2-Yl-3-(2-Methoxyphenyl)-prop-2-enyl]-6-oxo-1,6-dihydropyridine-2-carbonitrile

A density functional theory investigation of the mechanism of the titled reaction has been performed. The results suggest that the compound 1-[2-iodo-3-(2-methoxyphenyl)-prop-2-enyl]-6-oxo-1,6-dihydropyridine-2-carbonitrile would rather be converted into the titled free radical by deiodination than go by way of a Diels-Alder cycloaddition and HI-elimination to access the experimentally observed product. The deiodination of the radical precursor is followed by tandem radical cyclizations and hydrogen-loss oxidations to generate tetracyclic non-radical products. The mechanism of the tandem reaction was determined by an examination of the calculated reaction barriers, attack trajectories, and interaction energies between key orbitals. Furthermore, the H-loss oxidation of the addition intermediates by several H-abstractors were carefully analyzed. The theoretical results are in close agreement with the available experimental evidence. The detailed reaction mechanism and knowledge of such an intramolecular tandem radical cyclization presented in this study not only provide insight into the nature of tandem cyclizations but also serves as a useful guide for future experimental investigations.