Pyramidalization and Distortion Energies Control Rates of 1,3-Dipolar Cycloadditions With Phenyl Azide

Quantum mechanical calculations have revealed the role of alkene pyramidalization on reactivity in 1,3-dipolar cycloadditions. Ring strain arising from ground state angle distortion results in alkene pyramidalization. This study reports a computational investigation of azide cycloadditions to norbornene derivatives featuring pyramidalized double bonds. Quantum mechanical calculations were carried out with the M06-2X density functional. The alkene moieties of the norbornene derivatives are pyramidalized in the endo direction to relieve torsional strain, resulting in alkenes that are “pre-distorted” towards the favored exo transition state. The calculated activation barriers are strongly correlated with distortion energy and not with strain release. Slight deviations from planarity result in significant rate acceleration for the reactions studied. There is a strong correlation between ΔH^‡ and the extent of alkene pyramidalization. A 4º out-of-plane bending of the alkene correlates to a 1.4 kcal/mol lowering of ΔH^‡_, accelerating the reaction by an order of magnitude.