The generation and reactions of quinone methides

The combination of neutral non-aromatic and zwitterionic aromatic contributing valence bond structures confers a distinctive chemical reactivity to quinone methides, which has attracted the interest of a tremendous number of chemist and biochemists. This chapter reviews reactions that generate quinone methides, and the results of mechanistic studies of the breakdown of quinone methides in nucleophilic substitution reactions. The following pathways for the formation of quinone methides are discussed; (a) photochemical reactions; (b) thermal heterolytic bond cleavage; (c) reactions that unmask a quinone oxygen; (d) nucleophilic aromatic substitution reactions of water at 4-methoxybenzyl carbocations; (e) oxidation reactions of phenols; (f) reductive-elimination reactions of quinones; (g) miscellaneous reactions. Results, and their interpretation, of studies from the laboratories of A. J. Kresge and J. P. Richard are reviewed. The highlights include: (a) Experiments to characterize the effect of O-protonation and O-methylation of the p-quinone methide oxygen to form the p-hydroxybenzyl and pmethoxybenzyl carbocations, respectively, on electrophile stability and reactivity. (b) A comparison of p-quinone methide, o-quinone methide and o-thioquinone methide. (c) Evidence that structure-reactivity relationships for addition of nucleophiles to quinone methides closely resemble those determined for nucleophile addition to strongly resonance stabilized carbocations. (d) Evidence that the aromatic zwitterionic valence bond structure makes only a relatively small contribution to the structure of p-quinone methide. (e) A comparison of the Marcus intrinsic barriers for addition of water to p-quinone methide and to formaldehyde. (f) A discussion of the effect of O-methylation of p-quinone methide and formaldehyde on the intrinsic barrier for water addition.