The frontier molecular orbital (FMO) theory has provided a powerful model
for the qualitative understanding of reactivity and regioselectivity of the Cycloaddition
reactions, based on the electronic properties of isolated reactants. The 1,3-dipolar
cycloaddition reactions are explicable by the frontier molecular orbital approach, which
is based on the assumption that bonds are formed by a flow of electrons from the
highest occupied molecular orbital (HOMO) of one reactant to the lowest unoccupied
molecular orbital (LUMO) of another. But the tricky part here was to decide which
molecule supplied the HOMO and which supplied the LUMO. Furthermore, the
computational chemistry techniques like HOMOdipole-LUMOdipolarophile/HOMOdipolarophile-
LUMOdipole energy gaps, electronic chemical potentials (μ), electrophilicity indices (ω)
and the charge capacities (ΔNmax) are useful in indicating whether the reactions are
under normal or inverse electron demand conditions. Also, the relative kinetics of
cycloaddition reactions can be rationalized by utilizing HOMOdipole-LUMOdipolarophile
energy gaps and ΔNmax, from which it was found that increasing electron-withdrawing
power of the dipolarophile substituents, the energy gap decreases and, thus, reactions
with the same dipole became faster in Normal electron demand cycloadditions, while
the reverse occurs in case of inverse electron demand conditions.
Keywords: Cycloaddition, Chemical Potential, Charge Capacity, Diastereoselectivity,
Dipolarophile, Electrophilicity, Enantioselectivity, Inverse Electron
Demand Reactions, Normal Electron Demand Reactions, Regioselectivity,
Stereochemistry.