Computational elucidation of the reaction mechanism for synthesis of pyrrolidinedione derivatives via Nef-type rearrangement - cyclization reaction.

This paper reports a quantum chemical study of all stages of a one-pot synthesis of pyrrolidinedione derivatives from nitromethane and coumarin, which includes Michael addition, migration of an oxygen atom (Nef-type rearrangement), and cyclization to a pyrrolidine ring. The energy barrier of deprotonated nitromethane addition to coumarin is 21.7 kJ mol -1 , while the barrier of proton transfer from the methylene to the nitro group in the nitromethyl group is notably higher, 197.8 kJ mol -1 . The second stage of the reaction, migration of an oxygen atom within the nitromethyl group, occurs with lowest energy barrier, 142.4 kJ mol -1 , when it is assisted by an additional water molecule. The last stage - cyclization, passes with a very low energy barrier of 11.9 kJ mol -1 but the tautomerization of the nitrosohydroxymethyl group to the hydroxy- N -hydroxyiminomethyl, necessary for the process, has an energy barrier of 178.4 kJ mol -1 . Analogous calculations for the same process with the ethyl ester of 3-coumarin-carboxylic acid as substrate show that the relative energies of the intermediates and transition states are by at most 10-16 kJ mol -1 more stable than the corresponding structures with coumarin.