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

Abstract

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 (Aryl 2 CH + ) 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 diffusionlimited 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, s N ) 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 singleelectron transfer manifests that these reactions proceed via polar mechanisms.

Nucleophilic Reactivities of Thiophenolates

“…Despite the fact that such quantitative data on the nucleophilic reactivity of ArS – are at hand, the comparison of ArS – with other types of nucleophiles, even with analogously substituted phenolates (ArO – ), is hampered by a lack of kinetic data about ArS – reactivity toward common reference electrophiles.…”

Electrophilic reactivities of 7‐L‐4‐nitrobenzofurazans in σ‐complexation processes: Kinetic studies and structure–reactivity relationships

“…More recently, Mayr and coworkers 38 studied the ambident reactivity of a series of phenoxide anions toward benzhydrylium ion 15 and demonstrated that the activation barrier for oxygen attack is 20−30 kJ mol −1 lower than that for carbon attack. This results can be explained why the carbon‐bonded adducts 16, 16′, 17, and 17′ have not been observed in the present work.…”

Base‐free Enantioselective C(1)‐Ammonium Enolate Catalysis Exploiting Aryloxides: A Synthetic and Mechanistic Study

“…Key to this strategy is the multiple roles of the aryloxide within the catalytic cycle.I ti sr equired to be an effective leaving group for N-acylation, to act as aB rønsted base and aBrønsted acid (as the corresponding phenol), before acting as aL ewis base.T he steric and electronic effects of the aryloxide leaving group were examined to gain insight into the subtle effects that could alter its nucleophilicity,n ucleofugality and basicity ( Table 2). [15] Using para-nitrophenyl ester 7 allowed ester 13 to be isolated in high yield, dr and er (entry 1, 84 %, 84:16 dr, > 99:1 er). Reaction of pentafluorophenyl ester 8 gave product 14 in lower yield (39 %), although excellent stereocontrol was maintained (entry 2).…”