Ambident Reactivity of Phenolate Anions Revisited: A Quantitative Approach to Phenolate Reactivities

Prompted by the observation that
the regioselectivities of phenolate
reactions (C versus O attack) are opposite to the predictions by the
principle of hard and soft acids and bases, we performed a comprehensive
experimental and computational investigation of phenolate reactivities.
Rate and equilibrium constants for the reactions of various phenolate
ions with benzhydrylium ions (Aryl2CH+) and
structurally related quinone methides have been determined photometrically
in polar aprotic solvents. Quantum chemical calculations at the SMD­(MeCN)/M06-2X/6-31+G­(d,p)
level confirmed that O attack is generally favored under kinetically
controlled conditions, whereas C attack is favored under thermodynamically
controlled conditions. Exceptions are diffusion-limited reactions
with strong electrophiles, which give mixtures of products arising
from O and C attack, as well as reactions with metal alkoxides in
nonpolar solvents, where oxygen attack is blocked by strong ion pairing.
The Lewis basicity (LB) and nucleophilicity (N, sN) parameters of phenolates determined in this
work can be used to predict whether their reactions with electrophiles
are kinetically or thermodynamically controlled and whether the rates
are activation- or diffusion-limited. Comparison of the measured rate
constants for the reactions of phenolates with carbocations with the
Gibbs energies for single-electron transfer manifests that these reactions
proceed via polar mechanisms.