The theoretical rationale is presented for changes in reaction mechanism that are enforced by intermediate lifetimes, with an emphasis on the carbocation intermediates of nucleophilic substitution at aliphatic carbon. This powerful model is accessible to graduate students and provides a starting point for rationalizing the results of complex mechanistic studies in Physical Organic Chemistry.

The change from a stepwise to concerted reaction mechanism is favored by the destabilization of the stepwise reaction intermediate that is avoided in the concerted reaction. William Jencks provides many examples of changes from stepwise to concerted reaction mechanisms that are strictly enforced as the lifetime of the stepwise reaction intermediate approaches that for a bond vibration, and the energy well for the reaction intermediate disappears. An early prescient example of lifetime-enforced changes in the mechanism for general acid catalysis of addition of thiolate anions to acetaldehyde is presented. Examples of lifetime-enforced concerted nucleophilic substitution and elimination reactions at benzylic carbon and of nucleophilic substitution on α-alkoxy carbon are presented to illustrate the power of this model to rationalize changes in reaction mechanism. Controversies that have been clarified by a consideration of the lifetime of putative carbocation intermediates of stepwise nucleophilic substitution reactions are discussed. The influence of coupling motions of the nucleophile and nucleofuge at the transition state for concerted bimolecular nucleophilic substitution reactions on the dominant product from competing solvolysis and substitution reactions is considered. Physical organic chemists are encouraged to use this powerful model in designing experiments to rationalize changes in reaction mechanisms.