Reactivity of δ-Functionalized Para-Quinone Methides in Nucleophilic Addition Reactions.

The electrophilic reactivities of para-quinone methides (pQMs) with functional groups (FG) at the exocyclic polarized carbon-carbon double bond were determined by photometrically monitoring the kinetics of their reactions with carbanions in dimethyl sulfoxide (DMSO) at 20 °C. The experimental second-order rate constants k were evaluated by the Mayr-Patz equation, that is, the linear free energy relationship lg k = s(N + E), which was leveraged to determine the electrophilicity descriptors E of the pQMs. These electrophilicity parameters E were subsequently used to successfully predict the scope of the pQM reactions with C-, H-, N-, O-, and S-centered nucleophiles. Moreover, the electrophilicity parameters E correlate linearly with a linear combination of quantum-chemically calculated methyl anion affinities (MAAs) and buried volumes (%V). While MAA values mainly reflect the thermodynamic driving force of the carbon-carbon bond formation, %V values take account of the variable steric effects of substituents at the electrophilic δ-position of the pQMs. Knowledge of MAA and %V thus enables chemists to tailor novel pQMs with predictable reactivity properties.