1,3-Dipolar Cycloaddition - Reactivity

Reactivity

Concerted processes such as the 1,3-cycloaddition require a highly ordered transition state (high negative entropic energy) and only moderate enthalpy requirements. Using competition reaction experiments, relative rates of addition for different cycloaddition reactions have been found to offer general findings on factors in reactivity.

• Conjugation, especially with aromatic groups, increases the rate of reaction by stabilization of the transition state. During the transition, the two sigma bonds are being formed at different rates, which may generate partial charges in the transition state that can be stabilized by charge distribution into conjugated substituents.
• More polarizable dipolarophiles are more reactive because diffuse electron clouds are better suited to initiate the flow of electrons.
• Dipolarophiles with high angular strain are more reactive due to increased energy of the ground state.
• Increased steric hindrance in the transition state as a result of unhindered reactants dramatically lowers the reaction rate.
• Hetero-dipolarophiles add more slowly, if at all, compared to C,C-diapolarophiles due to a lower gain in sigma bond energy to offset the loss of a pi bond during the transition state.
• Isomerism of the dipolarophile affects reaction rate due to sterics. trans-isomers are more reactive (trans-stilbene will add diphenyl(nitrile imine) 27 times faster than cis-stilbene) because during the reaction, the 120° bond angle shrinks to 109°, bringing eclipsing cis-substituents towards each other for increased steric clash.