Theoretical revisit of regioselectivities of Diels-Alder reactions: Orbital-based reevaluation of multicentered reactivity in terms of reactive hybrid orbitals

When reactions proceed under kinetic control, stereoselectivities are determined from energetic properties of the transition state (TS). Orbital interaction at the TS plays a significant role in determining reactivity and selectivity, because it is directly related to lowering of the activation barrier. However, the orbital interaction at the TS cannot be represented only in terms of the frontier orbitals at the reactant state. A reactive hybrid orbital (RHO) that is localized at the reaction site is used to represent the orbital around the relevant TS in terms of a combination of the canonical molecular orbitals (MOs). This representation can make comparison of reactivities and selectivities among molecules of different sizes feasible. In this paper, the regioselectivities of Diels-Alder cycloaddition reactions of a monosubstituted butadiene and a dienophile (a monosubstituted ethylene) are investigated in terms of several parameters such as reactivity index and stabilization index, which are obtained on the basis of the newly developed multicentered version of the RHO method. These values can also be compared with the corresponding parameters defined on the basis of the frontier orbitals. Predictions of the regioselectivities based on the RHOs are consistent with experimental observations, while those based on the frontier orbitals are unreliable. This is because the RHO is superior to the frontier orbital as a descriptor of the orbital participating in orbital interactions around the TS.