The S_N2 Transition State. 6: Breakdown of the Reactivity–Selectivity Principle in the S_N2 Reaction of α‐Halocarbonyl Compounds. A Molecular Orbital Analysis [1]

A molecular orbital (MO) analysis of the S_N2 transition state (TS) of α‐carbonyl derivatives is described with various nucleophile leaving group pairs. On the basis of this analysis it is shown that the enhanced selectivity toward nucleophiles observed in α‐halocarbonyl compounds is directly associated with S_N2 rate enhancement. Both observations result from a stabilizing frontier orbital interaction between a high lying π‐type three center orbital along the reaction coordinate axis and the carbonyl π‐system. The magnitude of interaction is greater for more powerful nucleophiles, resulting in both greater reactivity as well as additional selectivity relative to simple alkyl halides.