Substituents on quinone methides strongly modulate formation and stability of their nucleophilic adducts

Emily E. Weinert, Ruggero Dondi, Stefano Colloredo-Melz, Kristen N. Frankenfield, Charles H. Mitchell, Mauro Freccero, Steven E. Rokita

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197 Scopus citations


Electronic perturbation of quinone methides (QM) greatly influences their stability and in turn alters the kinetics and product profile of QM reaction with deoxynucleosides. Consistent with the electron-deficient nature of this reactive intermediate, electron-donating substituents are stabilizing and electron-withdrawing substituents are destabilizing. For example, a dC N3-QM adduct is made stable over the course of observation (7 days) by the presence of an electron-withdrawing ester group that inhibits QM regeneration. Conversely, a related adduct with an electron-donating methyl group is very labile and regenerates its QM with a half-life of approximately 5 h. The generality of these effects is demonstrated with a series of alternative quinone methide precursors (QMP) containing a variety of substituents attached at different positions with respect to the exocyclic methylene. The rates of nucleophilic addition to substituted QMs measured by laser flash photolysis similarly span 5 orders of magnitude with electron-rich species reacting most slowly and electron-deficient species reacting most quickly. The reversibility of QM reaction can now be predictably adjusted for any desired application.

Original languageEnglish (US)
Pages (from-to)11940-11947
Number of pages8
JournalJournal of the American Chemical Society
Issue number36
StatePublished - Sep 13 2006

All Science Journal Classification (ASJC) codes

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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