Theoretical insight into the mechanism and selectivity of the [3+2] Cycloaddition Reaction of N-methyl-1-phenylmethanimine Oxide and Bicyclopropylidene with a MEDT Perspective

Abstract

AbstractThe mechanism and regioselectivity of [3+2] cycloaddition (32CA) reactions of N-methyl-1-phenylmethanimine oxide nitrone1and bicyclopropylidene2are analyzed using molecular electron density theory (MEDT) at the B3LYP/6-311++G(d,p) level. A study of the electron localisation function (ELF) predicts thezwitter-ionicnature of the nitrone, allowing its participation inzw-type32CA reactions with a high energy barrier that must be surmounted by suitable electrophilic–nucleophilic interactions. The global electronic flux from the strong nucleophilic bicyclopropylidene2to the electrophilic nitrone1is predicted by an analysis of the CDFT indices. In this 32CA reaction, no new covalent bonds are generated at the TSs, and the mechanism is one-step and kinetically controlled with low asynchronous bond production. The Gibbs free energy of this 32CA reaction in the gas phase is -9.88 and -15.01 kcal.mol-1forexoandendopath, respectively. The increased thermodynamic stability of the cycloadducts4favors theendoregiochemical route. The ELF topological examination at the transition stages is in agreement with the predictions of bonding evolution theory (BET) for theendoandexoroutes, which point to a one-step process including early transition states.