How Persistent Is Cyclopropyl upon Nucleophilic Substitution, and Is Frontside Displacement Possible? A Model Study

Quantum chemical model calculations (MP2/6-31G(d,p)) demonstrate that frontside nucleophilic substitution is not possible in the reaction between water and protonated cyclopropanol. Instead, ring opening occurs, in accordance with a well-known disrotary ring-opening mechanism. When the cyclopropane ring is embedded in a stabilizing bicyclic structure, as in protonated bicyclo[3.1.0]hexanol, the mechanistic landscape changes. In this case frontside nucleophilic substitution occurs, and has a potential energy barrier which is lower than that of the corresponding backside substitution, which implies that the stereochemical outcome of this gas-phase nucleophilic substitution reaction is uncoupled from its kinetic order. This and similar results challenge the traditional view that nucleophilic substitution reactions should be categorized as being either S_N1 or S_N2.