Transition-state structural variation and mechanistic change

An important link between theoretical and experimental views of organic reactivity is provided by More O'Ferrall-Jencks diagrams, which are commonly used in empirical discussions of reaction mechanisms and of changes in transition-state structure. We have performed semiempirical AM1 molecular-orbital calculations for S_N2 displacements on α-substituted alkyl substrates and for general acid-catalysed hydride reduction of a carbonyl group which demonstrate transition-state structural variations in accord with the predictions of these diagrams. We provide an example of a possible danger associated with the use of these diagrams in considerations of mechanistic change. We have examined the changeover in mechanism from S_N2 to S_N1 occuring in the degenerate reaction H₂O + CHR′R″OH₂⁺ → ⁺H₂OCHR′R″ + OH₂ as the α-substituents R′ and R″ are altered. The methyl (R′ = R″ = H) and ethyl (R′ = H, R″ = Me) substrates react by the S_N2 mechanism, whereas the isopropyl (R′ = R″ = Me), methoxymethyl (R′ = H, R″ = OMe) and methoxyethyl (R′ = Me, R″ = OMe) substrates follow the S_N1 mechanism. The mechanisms merge according to the classical model of Doering and Zeiss, with the S_N1 intermediate appearing with essentially the same structure and energy as the disappearing S_N2 transition state.