The peripheral attack model is based on predicting lowest energy conformations of an inherently complicated system, where nuanced perturbations can cause huge stereodifferentiating consequences.  By modeling peripheral attack using the Curtin-Hammett scenario depicted above, the transition state is excluded from this conformation analysis by assuming that the barrier to each transition state from a given conformation is the same and thus that ground state conformations are the sole product determining factor. A significant criticism is the mapping of medium-sized ring conformations and influences onto larger ring systems. Macrocycles can possess varying degrees of rigidity in their structure, making a single peripheral attack model difficult to apply to all systems.  Different classes of reactions might not fit the peripheral attack model, as reactions such as epoxidations, hydroxylations, alkylations, and reductions all proceed through different transition states.