Toward an understanding of the selectivity in domino reactions. A DFT study of the reaction between acetylenedicarboxylic acid and 1,3-bis(2-furyl) propane

The mechanism of the domino reaction between acetylenedicarboxylic acid and 1,3-bis(2-furyl)propane has been theoretically studied in the framework of density functional theory. This domino process comprises two consecutive c ycloaddition reactions: the first one is initialized by the nucleophilic at tack of the C5 position of the furan ring to a conjugate position of acetyl enedicarboxylic acid to give a zwitterionic intermediate, which by a subseq uent ring-closure process affords an oxanorbornadiene intermediate. The sec ond reaction is an intramolecular concerted cycloaddition of this intermedi ate to give the final dioxapentacyclic adduct. For the second cycloaddition , which corresponds to the step controlling the selectivity, eight alternat ive reaction pathways are found. Chemoselectivity, facial selectivity, and stereoselectivity of this domino reaction are related with the different ap proach modes of the tethered furan to the oxanorbornadiene system of the in termediate. The most favorable pathway takes place along an endo/syn approa ch of the furan ring relative to the bridged oxygen atom of the oxanorborna diene system, with participation of the substituted double bond. An analysi s of energetic contributions to the potential energy barriers for the intra molecular cycloadditions identifies the different factors controlling the r eactive channels. Selectivity outcome is reproduced by these calculations.