Phthalazine as a Diene in Diels – Alder Reactions with P‐ and As‐Containing Anionic Dienophiles: Comparison of Possible Reaction Channels

Abstract Phthalazine can behave as a diene in Diels–Alder (DA) cycloadditions, typically at the pyridazine ring, however, its application is somewhat limited because these reactions usually require harsh conditions or sophisticated catalysts. As an unconventional example, phthalazine was reported to undergo cycloaddition with the PCO − anion without any catalyst. In this computational study, we scrutinise the mechanism of the DA reactions between phthalazine and the so far known ECX − (E: P, As; X: O, S, Se) anions as dienophiles. In principle, the attack of an ECX − anion may occur at two different sites of phthalazine, either at the benzene or the pyridazine ring, and both of these possible reaction channels were juxtaposed on the basis of energetic aspects. In all of the investigated cases, the analysis of the energy profiles reveals a clear regioselectivity that favours the attack at the pyridazine ring. As a result, so far unprecedented 2‐pnictanaphth‐3‐olate analogues seem achievable as final products. Comparing the characteristics of these pathways allowed us to clarify the source of this regioselectivity: The pyridazine ring of phthalazine exhibits lower aromaticity than the benzene subring; therefore, in the DA step, the former ring shows a higher affinity toward a dienophile than the latter, leading to lower activation barriers. To further map the electronic and structural features of the cycloaddition steps, the local interactions evolving in the transition states were analysed and compared using global and local descriptors. In most aspects, the characteristics of both pathways were found to be rather similar, in contrast to the markedly differing activation barriers on the two routes.